Author Interviews, Biomarkers, Lymphoma / 14.08.2020 Interview with: Dr. Ivana Špaková Pavol Jozef Šafárik University Košice, Slovakia What is the background for this study? Response:  The background is the plenty of space for studying "waste metabolites" which tell us more about the metabolism of the whole body as well as about the metabolism of the smallest compartment - cell. So we decided to study what is the difference in urine spectra (absorbance, excitation, and emission spectra) in patients with malignant melanoma and healthy subjects without positive cancer history. What are the main findings? Response: The main findings are "discovery" (it is not true discovery because the target molecules or metabolites are known for decades) of molecules{metabolites which together describe the stage of malignant melanoma. These findings could be used for future tracking the patient's response for treatment or for tracking the previously treated patients for malignant melanoma and are healthy at the moment of sampling. (more…)
Author Interviews, Hematology, Lymphoma / 12.12.2019 Interview with: Genentech Priscilla White, spokesperson Senior Manager, Corporate Relations Genentech What is the background for this study? What are the main findings?
  • Response: Mosunetuzumab is a T-cell engaging bispecific antibody designed to target CD20-positive B-cell blood cancers, by binding to both CD20 (on the surface of B-cells) and CD3 (on the surface of T-cells).
  • Analyses from the ongoing Phase I/Ib GO29781 study indicate that mosunetuzumab can produce durable responses in patients who have relapsed or who are refractory to prior treatment(s), including those who have relapsed or who are resistant to CAR T-cell therapy.
  • Results from this dose-escalation study showed encouraging efficacy with an objective response rate (ORR) of 62.7 percent (n=42/67) in slow-growing Non-Hodgkin Lymphoma and 37.1 percent (n=46/124) in aggressive NHL across all dose levels assessed.
  • Additionally, data demonstrated a complete response (CR) rate of 43.3 percent (n=29/67) in slow-growing NHL and 19.4 percent (n=24/124) in aggressive NHL. CRs showed durability, with 82.8 percent (n=24/29) of patients with slow-growing NHL remaining in remission up to 26 months off initial treatment and 70.8 percent (n=17/24) of patients with aggressive NHL, remaining in remission up to 16 months off initial treatment.
  • Of the participants who received prior CAR T-cell therapy, the ORR was 38.9 percent (n=7/18), and 22.2 percent (n=4/18) achieved a CR.
  • Adverse reactions included cytokine release syndrome (CRS) in 28.9 percent of patients with 20.0 percent at Grade 1 and 1.1 percent at Grade 3. Grade 3 neurological adverse events occurred in 3.7 percent of patients.
Author Interviews, Hematology, Lymphoma / 10.12.2019 Interview with: Steven M. Horwitz, MD Memorial Sloan Kettering Cancer Center New York, NY What is the background for this study? Response: Relapsed or refractory Peripheral T-Cell Lymphoma (R/R PTCL) remains a disease of significant unmet medical need. Duvelisib is an oral dual inhibitor of PI3K-δ and PI3K-γ approved for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) after at least two prior therapies, relapsed or refractory follicular lymphoma (FL) after at least two prior systemic therapies, and is being developed for the treatment of additional hematologic malignancies including R/R PTCL. In early studies, we saw a suggestion of quite good activity of duvelisib as a single agent in a range of subtypes of T-cell lymphoma. The PRIMO study is an ongoing, multi-center, open-label, registration-directed Phase 2 study evaluating duvelisib in patients with R/R PTCL that is expected to enroll approximately 120 patients. The study includes both a dose optimization phase and an expansion phase. The Primo study will be sufficiently powered to give a much more precise estimate of the activity in peripheral t cell lymphomas. However, prior to initiating the main cohort we needed to first try to identify an optimal dose. That “dose optimization cohort” is the subject of our presentation here. (more…)
Author Interviews, Hematology, Lymphoma / 10.12.2019 Interview with: Prof. John Seymour, MBBS, Ph.D Lead investigator of the MURANO Trial Director. Department of Hematology at the Peter MacCallum Cancer Centre & Royal Melbourne Hospital in Australia What is the background for this study? What are the main findings?
  • MURANO is an international, multicenter, open-label, randomized Phase 3 study designed to evaluate the efficacy and safety of venetoclax in combination with rituximab compared with bendamustine in combination with rituximab in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL).
  • At this year’s American Society of Hematology (ASH) annual meeting, we presented results from the four-year updated analysis from the study, which showed an 81 percent reduction in the relative risk of disease progression or death in patients randomized to the chemotherapy-free, two year fixed-duration treatment course of venetoclax plus rituximab and higher rates of minimal residual disease (MRD)-negativity compared to the standard of care regimen, bendamustine plus rituximab.
  • The long-term data further support the sustained clinical benefit of fixed-duration treatment with venetoclax in combination with rituximab for this patient population.
  • The safety profile of the combination is consistent with the known safety profile of each individual therapy alone. There were no new serious safety issues observed in the MURANO study since the last update. 
Author Interviews, Hematology, Lymphoma / 07.12.2019 Interview with: Constantine Tam, M.D. Hematologist and Disease Group Lead Low Grade Lymphoma and CLL at Peter MacCallum Cancer Centre Victoria, Australia, and Lead study investigator of CAPTIVATE What is the background for this study? Response: The Phase 2 CAPTIVATE (PCYC-1142) clinical trial evaluated 164 patients younger than 70 years (median age of 58 years) with previously untreated CLL/SLL. Patients were planned to receive ibrutinib for 3 cycles, followed by 12 cycles of ibrutinib and venetoclax in combination. Ninety percent of patients was able to complete the planned therapy. MRD status was evaluated in PB after 6, 9, and 12 cycles and in BM after 12 cycles of the combination. (more…)
Author Interviews, Cancer Research, Lymphoma / 06.12.2019 Interview with: Dr. Matthew S. Davids MD MSC Associate Director of the Dana-Farber CLL Center Attending physician Lymphoma Program, Division of Hematologic Malignancies Dana-Farber   Dr. Jennifer Crombie MD Instructor in Medicine Harvard Medical School What is the background for this study? Response: New data from our investigator-sponsored Phase 1 study exploring duvelisib in combination with venetoclax will be presented at ASH on December 7. In relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), duvelisib plus venetoclax demonstrated promising clinical activity, a manageable tolerability profile, and identified a recommended Phase 2 dosing (RP2D) regimen.  (more…)
Author Interviews, Environmental Risks, JAMA, Lymphoma, Occupational Health, Toxin Research / 23.04.2019 interview with: Sylvain Lamure, MD, Hematologist, Principal Investigator Pascale Fabbro-Peray, MD, PhD , Epidemiologist, Senior Investigator University of Montpellier, France What is the background for this study? Response: Occupational exposure to pesticides is a well-documented associated factor for non-Hodgkin lymphoma. The main biological mechanisms of both pesticides and chemotherapy are genotoxicity and reactive oxygen species generation. Cellular adaptation among patients exposed to low doses of genotoxic and oxidative compounds might hinder chemotherapy efficiency in lymphoma patients. T hus, we have investigated the association of occupational exposure with response to immunochemotherapy and survival in the subgroup of diffuse large B cell lymphoma, whose treatment is standardized. (more…)
Author Interviews, Cost of Health Care, Hematology, J&J-Janssen, Lymphoma / 02.12.2018 Interview with: Murali Sundaram, MBA, Ph.D. Director of Real World Value and Evidence Oncology, Janssen What is the background for this study? Response: Ibrutinib is a novel Bruton's tyrosine kinase (BTK) inhibitor approved for the treatment of patients with newly diagnosed chronic lymphocytic leukemia (CLL). Ibrutinib is administered orally while standard of care (CD20 monoclonal antibody-based chemoimmunotherapy [CIT]) is administered intravenously. This difference in route of administration impacts what type of benefit covers these treatments (i.e., pharmacy benefit for oral ibrutinib and medical benefit for intravenous CIT). Previous studies evaluating the costs burden of patients treated with ibrutinib versus CIT did not include the full spectrum of real-world healthcare costs. (more…)
Author Interviews, Biomarkers, Cancer Research, Journal Clinical Oncology, Lymphoma, Stanford / 23.08.2018 Interview with: Dr. David Kurtz, MD/PhD, Instructor and Dr. Ash Alizadeh MD/PhD, Associate Professor Division of Oncology, Department of Medicine Stanford University Medical Center What is the background for this study? What are the main findings?  Response: This work investigates the utility of circulating tumor DNA - a type of liquid biopsy - in diffuse large B-cell lymphoma, the most common blood cancer in adults. Liquid biopsies are an emerging technology to track cancers from a simple blood draw. Here, using a cohort of over 200 patients from 6 centers across North America and Europe, we asked if circulating tumor DNA could be used to detect lymphoma in patients, and more importantly, could it be used to identify responders and non-responders.  (more…)
Abuse and Neglect, Dermatology, Leukemia, Lymphoma, Melanoma / 15.08.2018 Interview with: Clive S. Zent MD Professor of Medicine Director of Lymphoma/CLL Program Wilmot Cancer Institute University of Rochester Medical Center Rochester NY What is the background for this study? What are the main findings?  Response: Patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL) have an increased risk of all skin cancers including malignant melanoma. This study in a stable population of CLL patients managed by a regional referral center confirmed that melanoma was over 6 times more common in than in an age and sexed matched general population. Because of the proactive skin screening program at the University of Rochester Medical Center’s Wilmot Cancer Center, most melanomas (77%) were detected at earlier stages and were treated surgically with curative intent. One patient with CLL and metastatic melanoma had a sustained remission of both diseases on treatment with ibrutinib and pembrolizumab. (more…)
Author Interviews, Breast Cancer, JAMA, Lymphoma / 23.01.2018 Interview with: Dr. Mintsje de Boer, MD Resident plastic surgery Department of Plastic, Reconstructive and Hand-Surgery Maastricht University Medical Centre+, Maastricht the Netherland On behalf of the Netherlands BIA-ALCL Consortium: Daphne de Jong (Hematopathologist, VU university medical Center, Amsterdam, the Netherlands), Hinne Rakhorst (Plastic Surgeon, MST/ZGT, Enschede, the Netherlands) René van der Hulst (Plastic surgeon, MUMC+ Maastricht, the Netherlands) Flora van Leeuwen (Epidemiologist, Netherlands Cancer Institute, Amsterdam, the Netherlands), Jan Paul de Boer (Hemato-oncologist, Netherlands Cancer Institute, Amsterdam, the Netherlands) Lucy Overbeek (Database expert PALGA, Houten, the Netherlands), What is the background for this study? Response: Breast implants are one of the most commonly used medical devices worldwide. Associations with breast cancer, connective tissue diseases and auto-immune diseases have never been unequivocally supported. For lymphoma risk, this is different and several reports have suggested an association between breast implants and risk of anaplastic large cell lymphoma in the breast (breast-ALCL). Over the past few years, the number of women with breast implants reported with breast-ALCL has strongly increased. This has resulted in significant attention amongst medical professionals and women alike with publications in medical journals and lay press. In part due to the rarity of the disease and due to the lack of breast implant prevalence data in the population, the absolute risks of breast-ALCL are largely unknown, precluding evidence-based counseling about implants. In the Netherlands, we are in the unique position to be able to retrieve all diagnosed breastALCL since 1990 as well as appropriate population-based control groups from the Nationwide Network and Registry of Histo- and Cytopathology in the Netherlands (PALGA). This has allowed a formal epidemiological risk assessment study based on sufficient numbers. Moreover, using combined and complementary sources of information, we have been able to determine age- and calendar year-specific implant prevalence rates to determine reliable absolute risks. This study could be successfully performed thanks to a multidisciplinary taskforce consisting of plastic surgeons, hematopathologists, epidemiologists, hemato-oncologists and radiologists from the several large institutions in the Netherlands  (more…)
Author Interviews, Gastrointestinal Disease, JAMA, Lymphoma / 08.11.2017 Interview with: ANSMRosemary Dray-Spira, MD, PhD Department of Epidemiology French National Agency for Medicines and Health Products Safety (ANSM) Saint-Denis, France What is the background for this study? What are the main findings? Response: Anti-tumor necrosis factor (anti-TNF) agents are increasingly used for the management of inflammatory bowel diseases (IBD), either alone or in combination with thiopurines. Their clinical benefits have been largely assessed, however they may expose to potentially serious adverse effects. While an increased risk of lymphoma has been established with thiopurines, up to now such a risk of lymphoma remained uncertain with anti-TNF agents. In this study based upon a large, nationwide cohort of 189,289 patients with IBD, the use of anti-TNF agents alone was found associated with a 2 to 3 fold increase in the risk of lymphoma, similarly to thiopurines alone. In addition, the combination of these two treatments was associated with a 6 fold increase in the risk of lymphoma, ie a higher risk than with each treatment used alone. Although these differences are statistically significant, the risk of lymphoma among patients exposed to anti-TNF agents is less than 1 case per 1000 person-years. (more…)
Author Interviews, Immunotherapy, Lymphoma, Pharmacology / 14.08.2016 Interview with: Dirk Huebner, MD Senior Medical Director Oncology Therapeutic Area Unit Takeda Pharmaceutical Company What is the background for this study? What are the main findings? Response: Cutaneous lymphomas are a category of non-Hodgkin lymphoma that primarily involve the skin. Cutaneous T-cell lymphoma, also known as CTCL, is the most common type of cutaneous lymphoma and typically presents with red, scaly patches or thickened plaques of skin that often mimic eczema or chronic dermatitis. ADCETRIS® (brentuximab vedotin) is an antibody-drug conjugate directed to CD30, which is expressed on skin lesions in approximately 50 percent of patients with CTCL. The Phase 3 ALCANZA trial compared the use of single-agent ADCETRIS to a control arm of investigator’s choice of standard therapies, methotrexate or bexarotene, in 131 patients with CD30-expressing CTCL who received prior systemic or radiation therapy. The study met its primary endpoint, demonstrating a highly statistically significant improvement in the rate of objective response lasting at least four months (ORR4). The ORR4 was 56.3 percent in the ADCETRIS arm compared to 12.5 percent in the control arm. (more…)
Author Interviews, Cancer Research, Genetic Research, Lancet, Lymphoma / 29.07.2016 Interview with: Jin-Xin BEI, Ph.D. Principal Investigator State Key Laboratory of Oncology in South China Sun Yat-sen University Cancer Center Guangzhou China What is the background for this study? Response: Natural killer T-cell lymphoma (NKTCL) is a rare and aggressive malignancy with remarkable prevalence in Asian and Latin populations, suggesting that the heritable components contribute to the disease risk. Epstein-Barr virus (EBV) infection has been thought to be major factor associated with NKTCL, and EBV DNA load in plasma has been applied in clinical managements, including diagnosis, treatment response and prognosis. However, the genetic component leading to NKTCL predisposition has not been identified. (more…)
Author Interviews, Cancer Research, CT Scanning, Lymphoma, NEJM / 23.06.2016 Interview with: Peter Johnson MA, MD, FRCP Professor of Medical Oncology Cancer Research UK Centre Southampton General Hospital Southampton What is the background for this study? What are the main findings? Prof. Johnson: Based upon retrospective series looking at the ability of interim PET to predict the outcomes of treatment, we aimed to test the idea of modulating treatment in response to an early assessment of the response to ABVD: could we safely reduce the amount of treatment by omitting bleomycin in the group who had responded well? Although the risk of severe toxicity from bleomycin is generally low, for the small number of patients who experience it, it can be life-changing or even fatal. We also wanted to test whether it might be possible to reduce the use of consolidation radiotherapy by comparison to our previous trials, and this seems to have worked too: we used radiotherapy in less than 10% of patients in RATHL, as compared to around half in our previous trials. We have seen better survival figures than in our previous studies with less treatment overall, so it feels as though we are on the right track. (more…)
ASCO, Author Interviews, Cancer Research, Geriatrics, Lymphoma, NYU, Pharmacology / 07.06.2016 Interview with: Dr. Catherine S. M. Diefenbach MD Assistant Professor of Medicine NYU Cancer Center New York, NY 10016 What is the background for this study? What are the main findings? Dr. Diefenbach: It is well known that age is important prognostic factor in non-Hodgkin’s lymphoma (NHL). Multiple studies have illustrated that elderly lymphoma patients have inferior survival outcomes as compared to their younger counterpart. While the tumor biology is often different in these two groups, and may play a role in this discordancy, elderly patients are often frail or have multiple medical comorbidities. These include geriatric syndromes, such as: cognitive impairment, falls, polypharmacy, and potentially inappropriate medication (PIM) use. All of these may contribute to poor outcomes for elderly patients. In addition, elderly patients are often under-treated for their aggressive lymphoma out of concern for toxicity or side effects, even though the data clearly demonstrates that elderly patients can still benefit from curative intent chemotherapy. (more…)
Author Interviews, Breast Cancer, Cancer Research, JNCI, Lymphoma / 03.03.2016 Interview with: David Hodgson, MD, MPH, FRCPC Associate Professor University of Toronto Toronto, ON Canada What is the background for this study? Dr. Hodgson: We know that treatment for childhood Hodgkin lymphoma can cause some side effects that arise years after treatment is  finished. In particular, radiotherapy given to the chest of adolescent females increases the risk of developing breast cancer in young adult survivors. But there are very little data about whether the early initiation of breast cancer screening will prevent breast cancer deaths in these survivors, and what kinds of screening is optimal. This is important because less than half of these young survivors are undergoing breast cancer screening, and in some jurisdictions early screening is not covered by insurance. What are the main findings? Dr. Hodgson: Because there has not been, and likely never will be, a large randomized screening trial for these patients, we used all the available information about their breast cancer risk, other health issues and the effectiveness of screening, and created a mathematical model that allows us to estimate the number of breast cancer deaths prevented by starting screening at age 25 for women who had received chest RT as teenagers. We found that one would have to invite about 260 survivors to early mammographic screening to prevent one breast cancer death, which compares favorably to other accepted reasons for breast cancer screening. Using MRI for screening, approximately 80 women would have to be invited to prevent one breast cancer death, because MRI is so much more sensitive than mammography. One of the problems with MRI, however, is that a substantial number of women will have "false positive" tests - abnormal findings that are not really cancer. (more…)
AACR, Author Interviews, Cancer Research, Lymphoma / 03.02.2016 Interview with: Theresa Keegan, PhD, MS Associate Professor Division of Hematology and Oncology UC Davis Comprehensive Cancer Center Sacramento, California 95817 Medical Research: What is the background for this study? What are the main findings? Dr. Keegan: This study expanded upon our earlier work examining survival among the young population diagnosed with Hodgkin lymphoma, which can be cured about 90 percent of the time with it is diagnosed at its earliest stages.  We tracked 9,353 patients ages 15-39 who were diagnosed with Hodgkin lymphoma between 1988 and 2011. Using California Cancer Registry data, we examined the impact on survival of socio-demographic characteristics such as race/ ethnicity, neighborhood socioeconomic status (SES), health insurance, the types of treatment patients received and whether they were diagnosed with subsequent cancers. We found that insurance coverage, neighborhood socioeconomic status (SES) and the types of treatment provided patients all played a role in survival.  Young adults diagnosed with early-stage Hodgkin lymphoma were twice as likely to die if they resided in a lower SES neighborhood. They were also twice as likely to die if they had public health insurance or were uninsured, whether they were diagnosed at an early stage or late stage. While there were improvements in survival over time, disparities in survival persisted for some racial/ethnic groups. African American patients were 68 percent more likely to die of their disease than non-Hispanic white patients, regardless of stage at diagnosis. Hispanic AYA patients diagnosed at a late stage were 58 percent more likely than non-Hispanic white patients to die of Hodgkin lymphoma; there was not a significant disparity for Hispanic patients diagnosed at an early stage. (more…)
ASCO, Author Interviews, Cancer Research, Lymphoma / 18.01.2016

More Cancer Research on Interview with: Erin E. Hahn, PhD, MPH Research Scientist Southern California Permanente Medical Group Kaiser Permanente Research Department of Research & Evaluation Pasadena, CA 91101 Medical Research: What is the background for this study? Dr. Hahn:  Adolescent and young adults, or AYAs, who are diagnosed and treated for Hodgkin lymphoma have very high overall survival rates. However, these patients are at high risk for short and long term health issues related to their cancer treatment, including cancer recurrence, cardiac and pulmonary problems, and developing new primary cancers. Some of these issues arise during treatment and persist over time, called long-term effects, and some develop years later, called late effects. Evidence and consensus based guidelines are available from organizations like the National Comprehensive Cancer Network and the Children’s Oncology Group to help manage the post treatment care of  Adolescent and young adults Hodgkin lymphoma survivors. Examining adherence to guidelines is an important part of high quality care, and can help us find and address gaps in care. Guideline recommended care for these patients includes: oncology visits, imaging and labs, preventive care, counseling and education, risk based screening for late effects. Risk-based screening is based on a patient’s treatment. The type of health screening a patient needs is determined by the treatment exposure they had, such as certain types of chemotherapy or high-dose radiation that have known late effects  Medical Research: What are the main findings? Dr. Hahn: For this pilot study, I was interested to see if post-treatment  Adolescent and young adults Hodgkin lymphoma patients in an integrated health care system received recommended short and long term care. The study setting is Kaiser Permanente Southern California (KPSC). KPSC provides care for almost 4 million members with 14 medical centers, and they have a long-standing electronic medical record. For our population, we included AYA patients diagnosed with classical Hodgkin lymphoma between 15 and 39 years of age, diagnosed between 2000 and 2010. We wanted to find patients who were diagnosed, treated, and followed for at least 2 years within this single system. We have a sample of 354 patients, which is great. It has been traditionally difficult to find and follow these patients/obtain accurate medical information that isn’t only self-report data. We were able to extract chemotherapy, radiation, and other care details from the electronic medical record. We first looked at receipt of short term recommended care, within the first year after treatment had ended. We looked specifically at oncology visits, use of recommended CT scan and lab tests, and preventive care, such as the flu vaccine. The great majority of patients had the recommended oncology visits, CT scan, and lab tests. However, receipt of the flu vaccine was lower, at 20%. When we looked at a composite measure of all 4 recommended services, only about half of the patients received all four recommended services within the first year after treatment. We also looked at use of a longer term recommended service for cardiac issues. Cardiac screening is recommended for patients who are 10 years out from their treatment and who received high-dose anthracyclines, plus radiation to the chest. This is the highest risk group for cardiac damage. Almost everyone received annual blood pressure screening, but only about 30% received screening with an electrocardiogram, echocardiogram, or MUGA scan. (more…)
Author Interviews, Cancer Research, Lymphoma, NEJM / 24.12.2015 Interview with: Dr. Michael van Leeuwen PhD Department of Epidemiology Netherlands Cancer Institute Amsterdam, the Netherlands Medical Research: What is the background for this study? What are the main findings? Response: Over the last decades cure rates for Hodgkin’s lymphoma patients have increased dramatically. Cure and long-term survival may, however, come at a price, in the form of an increased risk of second cancers and other late effects. Since the late 1980’s treatment of Hodgkin’s lymphoma has been changed towards smaller radiation target volumes and more effective, generally less toxic chemotherapy. In a study which included 3905 Hodgkin’s lymphoma patients treated between 1965 and 2000 in the Netherlands, the impact of these treatment changes on second malignancy risk was evaluated. Hodgkin’s lymphoma patients were between the ages of 15 and 50 years and had survived at least 5 years after treatment. During follow-up, 1055 second cancers were diagnosed in 908 survivors, corresponding to a risk of 4.6 times as high as the occurrence of cancer in the general population. Up to at least 40 years after treatment for Hodgkin’s lymphoma, survivors remained at increased risk for second cancers. The cumulative incidence of a second cancer was 33.2% at 30 years, compared with 9.6% in the general population, and 48.5% at 40 years, compared with 19.0% in the general population. Breast cancer was the most common second cancer reported followed by lung and gastrointestinal cancers. Thirty-year cumulative incidence was 16.6% for breast cancer, 7.1% for lower respiratory tract cancers, 7.0% for gastrointestinal cancers, and 3.7% for non-Hodgkin’s lymphomas. The risk of solid cancer after treatment for Hodgkin’s lymphoma was not lower among more recently treated patients (patients treated between 1989 and 2000) than among those who were treated in earlier time periods, despite changes in treatment. Nonetheless, patients treated with smaller radiation fields (e.g., a supradiaphragmatic field radiotherapy not including the axilla) were at a 63% lower relative risk of breast cancer as a second malignancy than if they received complete mantle-field radiotherapy. The lack of change in the cumulative incidence of solid cancers could be due to an incomplete adoption of the more modern radiotherapy concepts but may also be explained on the basis of a change in the chemotherapy regimens used in the 1990s. Because in the 1970’s many women exposed to high doses of alkylating agents were experiencing premature menopause, doses of alkylating agents were lowered over time to preserve fertility. However, early menopause introduced with the alkylating regimens was likely responsible for decreasing the breast cancer incidence. With the lower doses of the alkylating agents, this protection was taken away. The cumulative incidence of non-Hodgkin’s lymphoma and of leukemia (and the myelodysplastic syndrome) was, however, much lower among patients who were treated in the period from 1989 through 2000 than among those who were treated in the period from 1965 through 1976. For leukemia, the decrease in cumulative incidence is likely due to the much lower doses of alkylating agents used in Hodgkin’s lymphoma treatment in the 1990’s compared to earlier decades. It is important to realize that current common practice in radiation oncology, including involved-node or involved-site radiotherapy, three-dimensional conformal radiation treatment planning, and radiation doses of less than 36 Gy, was not applied in our study population. It is hoped that these changes may reduce the risk of solid cancer among patients treated after 2000. (more…)
Author Interviews, Immunotherapy, Lymphoma, NYU / 11.12.2015 Interview with: Dr. Catherine S. M. Diefenbach MD Assistant Professor of Medicine NYU Langone Laura and Isaac Perlmutter Cancer Center New York, NY 10016  Medical Research: What is the background for this study? What are the main findings? Dr. Diefenbach: The background of the study is that through an understanding of the unique immunobiology of Hodgkin lymphoma we can derive rational treatment strategies which may heighten the efficacy of existing therapies, and improve the outcomes for patients with relapsed disease.  In E4412 which is a national study sponsored by the Eastern Cooperative Oncology Group (ECOG-ACRIN) we explore the safety and efficacy of combination of the antibody drug conjugate brentuximab vedotin which targets CD30 on the surface of the Hodgkin lymphoma tumor cells, and immune stimulation of the T cells in the tumor microenvironment using checkpoint inhibitors.  We reported the data from the first arm of the study Brentuximab Vedotin and Ipilimumab.  To date 23 patients with relapsed Hodgkin lymphoma have been treated; the combination of brentuximab and ipilimumab was safe and well tolerated with primarily grade 1 and 2 toxicities.  In 18 patients evaluable for response the ORR was 72% with a complete response rate of 50%. (more…)
AACR, Author Interviews, Lymphoma, MD Anderson / 12.11.2015 Interview with: Dr. Jatin J. Shah, MD Associate Professor, Department of Lymphoma/Myeloma Assistant Professor, Lymphoma/Myeloma Division of Cancer Medicine The University of Texas, MD Anderson Cancer Center Houston, TX  Medical Research: What is the background for this study? What are the main findings? Dr. Shah: The ubiquitin-proteasome system (UPS) is one of the key regulatory systems in our body’s cells. It controls the destruction of the majority of cellular proteins, which can be involved in making cells grow, expand, or die, among other functions. Defects in the UPS can result in a number of diseases, including cancer, for example by destroying too quickly the proteins that cause cells to die. The UPS has already been shown to be a rational target for cancer therapy: the approved drugs bortezomib and carfilzomib inhibit the proteasome itself, thus causing cancer cells to die. However, by completely blocking the proteasome, which is at the ‘end’ of the UPS, these drugs block the destruction of 100% of proteins, and can cause side effects. By contrast, blocking the NEDD8-activating enzyme (NAE) stops the cellular processes that are responsible for only approximately 20% of proteins being degraded by the UPS – including proteins of relevance to cancer development. Previous studies of pevonedistat in animals have shown that inhibiting NAE alters the ability of a cancer cell to repair its DNA after it is damaged; this leads to the death of cancer cells. The man finding is this was the first reported study of pevonedistat in patients with multiple myeloma or lymphoma. It demonstrated that pevonedistat hits its target in cancer cells, exerted anticipated pharmacodynamic effects, and has modest activity as a single-agent in heavily pretreated patients with relapsed/refractory lymphoma. (more…)
Author Interviews, Chemotherapy, Lymphoma, NEJM / 04.11.2015

Jia Ruan, M.D., Ph.D. Associate Professor of Clinical Medicine Weill Cornell Medicine Lymphoma Program Division of Hematology & Medical Oncology New York, NY Interview with: Jia Ruan, M.D., Ph.D. Associate Professor of Clinical Medicine Weill Cornell Medicine Lymphoma Program Division of Hematology & Medical Oncology New York, NY 10021   Medical Research: What is the background for this study? What are the main findings? Dr. Ruan: Mantle cell lymphoma is an uncommon subtype of non-Hodgkin lymphoma that primarily affects elderly populations. Conventional chemotherapy regimens are generally not curative, and may not be tolerated by many patients, underscoring the need for treatment alternatives.  Previous experience with immunomodulatory compound lenalidomide has shown favorable activity and was well tolerated in patients with relapsedMantle cell lymphoma.  We evaluated the efficacy and safety of the biologic combination with lenalidomide plus rituximab as initial treatment for mantle-cell lymphoma (MCL). The main findings of the study showed that the combination was effective and generally well tolerated when given as induction and maintenance treatment. The overall response rate was 92%, with complete response rate of 64% in the 36 evaluable patients. Median duration of response has not been reached at a median follow up of 30 months.   Treatment was outpatient-based and quality-of-life was preserved for most patients. (more…)
Author Interviews, Infections, Lymphoma / 16.10.2015 Interview with: Matthieu Million, MD, PhD Assistant of Professor RAOULT French National referral center for Q fever Service de Maladies Infectieuses du Professeur BROUQUI Chemin des Bourrely Marseille Medical Research: What is the background for this study? What are the main findings? Dr. Million: Human lymphomas have been associated with many infectious agents including viruses (HCV, HIV) but also bacteria (Helicobacter pylori). Q fever, the infection by Coxiella burnetii, mainly acquired from domestic (cattle, sheep, goats but also dog and cats) or wild animals (deer), has been associated with many lymphoproliferative disorders (hyperlymphocytosis, mononucleosic syndrome). We observed a lymphoma developing in a patient followed up for Q fever that prompted us to investigate the association between the two diseases. In this study, we reported 11 cases of B-cell lymphoma developing after Coxiella burnetii primary-infection, we found an increased incidence of lymphoma in Q fever patients, particularly those with persistent focalized infection, and we detected the viable bacterium within lymphoma tissues. More specifically, we found that this bacterium infect the plasmacytoid dendritic cells (pDCs) in patients with C. burnetii-related lymphoma. This is particularly important since these cells are critical modulating their immune microenvironment including the natural antitumoral activity. Moreover, we found that peripheral blood mononuclear cells of these patients overproduce interleukin-10 even in the absence of the bacterium. This suggests that a persistent reprogramming of their immune cells have been triggered by the infection. Finally, we showed that these patients have very high levels of the anti-inflammatory Interleukin-10 in their serum, suggesting a systemic immune escape favoring the development of cancer. Coxiella burnetii is associated with an increased risk of lymphoma, its presence in the tumor microenvironment may favor lymphomagenesis. C. burnetii should be added to the list of bacteria that promote human B-cell non-Hodgkin lymphoma. (more…)
Author Interviews, Cancer Research, Leukemia, Lymphoma / 17.09.2015

Angelica Loskog, PhD Professor of Immunotherapy (adjunct) Dept of Immunology, Genetics and Pathology Uppsala University Uppsala Interview with: Angelica Loskog, PhD Professor of Immunotherapy (adjunct) Dept of Immunology, Genetics and Pathology Uppsala University Uppsala Sweden Medical Research: What is the background for this study? What are the main findings? Dr. Loskog: CAR T cells have shown remarkable effect in patients with B cell malignancy in the US using 2nd generation CAR T cells. Acute leukemia (ALL) seems easier to treat than lymphomas and one of the reasons may be difficulties for CAR T cells to penetrate a solid lesion or due to a higher local presence of immunosuppressive cells within a lesion. As one of the first centers outside US we are evaluating 3rd generation CAR T cells in both lymphoma and ALL aiming to compare the responses and investigating biological reasons for the different responses. So far we have treated 11 patients and 6 of them had initial complete responses. Unfortunately, some progressed later. (more…)
Author Interviews, Dermatology, Lymphoma / 12.08.2015 Interview with: Alain H. Rook, M.D. Professor of Dermatology University of Pennsylvania Philadelphia, PA 19104 and Rachael A. Clark, M.D., Ph.D. Department of Dermatology Brigham and Women's Hospital Boston, MA 02115   Researchers’ summary: In this paper, Dr. Rachael Clark and I describe a novel topical therapy for mycosis fungoides (MF), which is a skin-limited variant of cutaneous T-cell lymphomas (CTCL), a group of non-Hodgkin's lymphomas which represent cancers derived from skin-homing T cells. Although therapies exist that suppress the inflammatory skin lesions of MF, there are no curative therapies for this otherwise lifelong disease except for stem cell transplantation, which is only carried out in patients with aggressive and progressive disease. This manuscript describes a phase I trial of a novel immunomodulatory compound called resiquimod. This molecule stimulates two key receptors TLR7 and TLR8. Unlike imiquimod, a similar compound that is FDA approved for the treatment of local skin cancers, resiquimod actually stimulates inflammatory cytokine release from the dendritic cells that populate both healthy and inflamed human skin. As a result, this drug can enhance antigen presentation and immune responses. This study demonstrated that topical resiquimod was remarkably effective in that 90% of patients experienced a decrease in the percentage of the malignant T cell clone in skin lesions, and two patients had complete clearance of all disease, including both the treated skin lesions and the untreated lesions. To our knowledge, this is the first demonstration of regression of untreated skin lesions using a topical medication. This suggests that systemic antitumor immunity develops in these patients. Translational studies on the skin before and after treatment showed that the malignant T cell clone declined and inflammatory cytokine production by benign T cells increased after therapy suggesting the medication enhanced antitumor responses. In summary, this manuscript describes a small phase I trial that showed that topical resiquimod is safe, effective therapy for mycosis fungoides and can cause regression of both treated and untreated skin lesions, and may therefore represent a long-term potential cure for this otherwise lifelong disease. (more…)
Author Interviews, Lymphoma, Nutrition / 27.07.2015

Mara Meyer Epstein, ScD Assistant Professor Meyers Primary Care Institute University of Massachusetts Medical Interview with: Mara Meyer Epstein, ScD Assistant Professor Meyers Primary Care Institute University of Massachusetts Medical School MedicalResearch: What is the background for this study? What are the main findings? Dr. Epstein: Hodgkin lymphoma is a relatively rare cancer, with about 9,000 new cases diagnosed in the US each year. Hodgkin lymphoma is most commonly diagnosed in earlier (aged 15-34 years) or later adulthood (aged ≥50 years). The causes of the disease are not well understood, and most identified risk factors are not modifiable (for example, age, sex, family history, and infection with Epstein-Barr virus [EBV]). Previous studies have suggested that chronic inflammation may play a role in the development of Hodgkin lymphoma. Therefore, it is possible that a factor that can influence inflammation, such as diet, may be associated with risk of Hodgkin lymphoma. Discovering modifiable risk factors for Hodgkin lymphoma could offer a means for preventing this disease. The few existing studies of diet and Hodgkin lymphoma risk have focused on individual nutrients or foods; this is the first study to examine dietary pattern and risk of Hodgkin lymphoma. By examining dietary patterns instead of individual foods, we sought to assess Hodgkin lymphoma risk from the food combinations that may more closely reflect typical dietary habits. The current study includes 435 cases of Hodgkin lymphoma and 563 controls with no history of cancer from Massachusetts and Connecticut who were enrolled in the study between 1997 and 2000. Cases and controls provided information about their average intake of 61 food and beverage items over the year prior to the study. By evaluating foods commonly consumed by the study participants, we identified four major dietary patterns; high vegetable intake, high meat intake, high intake of fruit and low-fat dairy, and high intake of desserts and sweets. We looked for associations between each dietary pattern and risk of Hodgkin lymphoma overall, and also separately by age group (<50 years or ≥50 years old), tumor EBV status (positive or negative), and by tumor cell pattern (nodular sclerosis or mixed cellularity). The dietary pattern characterized by high intake of desserts and sweets was associated with a statistically significant increased risk of Hodgkin lymphoma among younger adults, and in particular, a 2-fold increased risk among younger adults with EBV-negative tumors. The dietary pattern featuring high meat intake was associated with a 3-fold increased risk of Hodgkin lymphoma among older adults, and again, we saw a stronger association among older adults with EBV-negative tumors, although the number of such cases in this group was small. We did not observe a clear association between the high vegetable dietary pattern, or the dietary pattern high in fruit and low-fat dairy intake, with Hodgkin lymphoma risk, and we also did not find any clear associations with EBV-positive tumors, which were relatively infrequent in the study population. The findings described above were obtained from statistical calculations that also took into account known Hodgkin lymphoma risk factors, other lifestyle factors, total caloric intake, and body mass index. (more…)
Author Interviews, Lancet, Lymphoma / 17.07.2015

MedicalRDr Yeow Tee Goh Department of Haematology Singapore General Hospital Republic of Interview with: Dr Yeow Tee Goh MBBS Department of Haematology Singapore General Hospital Republic of Singapore Medical Research: What is the background for this study? What are the main findings? Dr. Goh: Relapsed or refractory peripheral T-cell lymphoma after conventional chemotherapy is associated with a very poor prognosis and there is currently no recommendation on the standard approach to helping these patients. Novel targeted treatments for relapsed or refractory peripheral T-cell lymphoma such as romidepsin, pralatrexate, belinostat, and brentuximab vedotin has been approved by the US Food and Drug Administration (FDA) based on the results of their Phase II studies. With the exception of the remarkable efficacy of brentuximab vedotin in systemic anaplastic large cell lymphoma (86% of patients responding to treatment), the efficacy of romidepsin, pralatrexate, and belinostat in relapsed or refractory peripheral T-cell lymphoma is only modest with objective response rates between 25% and 29%. To our knowledge, no other clinical study has reported on the use of novel combination of targeted agents in in relapsed or refractory peripheral T-cell lymphoma. In our study, Of 23 patients assessable for responses, 10 (43%, 95% CI 23–63) patients had an objective response, of which 5 were complete responses. The combined proteasome and histone deacetylase inhibitor treatment shows promising activity for patients with peripheral T-cell lymphoma. (more…)
Author Interviews, Lancet, Leukemia, Lymphoma, Occupational Health / 01.07.2015 Interview with: Dr Klervi Leuraud, Epidemiologist Institute for Radiological Protection and Nuclear Safety Cedex, France MedicalResearch: What is the background for this study? What are the main findings? Dr. Leuraud: INWORKS was performed to quantify the risk of cancer mortality associated to protracted low doses of ionizing radiation typical of occupational or environmental exposures, as well as of diagnostic medical exposures. While such risks are well known for acute exposures as those experienced by the Japanese survivors of the A-bombs, there is still a lack of information for exposures experienced by the workers and the public. Our study confirms the existence of an association between leukemia mortality and chronic exposure to low doses received by nuclear workers. (more…)
Author Interviews, Cancer Research, Exercise - Fitness, Lymphoma / 02.05.2015 Interview with: Terry Boyle, PhD CIHR Fellow, MSFHR Trainee, Honorary UBC Killam Fellow Cancer Control Research, BC Cancer Agency School of Population and Public Health, The University of British Columbia Australian NHMRC Early Career Fellow The University of Western Australia Cancer Control Research, BC Cancer Agency Vancouver BC Canada Medical Research: What is the background for this study? What are the main findings? Dr. Boyle : Little is known about what causes non-Hodgkin lymphoma (NHL), so trying to identify risk factors is particularly important for the prevention and control of this cancer. There is really good evidence that people who are physically active have a lower risk of some cancers (such as colon and breast cancers), but not many studies have investigated whether being physical active is associated with the risk of non-Hodgkin lymphoma. The key finding of this case-control study was that study participants who were in the higher (second, third, and fourth) quartiles of vigorously intense physical activity performance in their lifetimes had about 25 percent to 30 percent lower risk for NHL, compared with those who were in the lowest (first) quartile of vigorously intense physical activity. (more…)