AACR, Author Interviews, Cancer Research / 19.12.2019

MedicalResearch.com Interview with: Dr. Samir Parekh, MBBS Associate Professor Medicine, Hematology and Medical Oncology Icahn School of Medicine at Mount Sinai MedicalResearch.com: What is the background for this study? Would you briefly describe what is meant by 'neoantigens'? How might they be used to stimulate immunity in a multiple myeloma patients?  Response: Myeloma is considered a “cold” tumor for immunotherapy (as compared to some solid tumors such as melanoma) given the relatively fewer DNA mutations in an average myeloma patient. Our clinical experience suggests that this may not be totally correct.  Our findings focus on mutations that can become antigens (neo-antigens) and challenges the stereotype. We can create vaccines based on peptides resulting from these mutations to stimulate immune responses. (more…)
Author Interviews, Cancer Research, Hematology, J&J-Janssen / 04.12.2018

MedicalResearch.com Interview with: Caroline McKay, PhD Real World Value & Evidence, Oncology Janssen Scientific Affairs MedicalResearch.com: What is the background for this study? What are the main findings? Response: Considering patient preferences in treatment decision-making in oncology is growing in importance. While recent introduction of new treatments for multiple myeloma have improved survival and the possibility of sustaining longer remission periods, regimen options still vary with respect to efficacy, safety, and dosing. Therefore, patients and providers must consider tradeoffs inherent in making treatment decisions that are growing in complexity. Despite this, there is a lack of research describing patient preferences within the context of currently available treatment regimens. To address this gap, this study examined how multiple myeloma patients evaluate, or weigh, treatment options. Key findings from the research are that treatment preferences do not appear to be static, but instead suggest that the relative importance of treatment attributes may change over time and treatment history. Further, patients place higher importance on overall survival and progression-free survival than other treatment attributes, and may be willing to accept an increase in the risk of serious side effects and reduced convenience in exchange for greater efficacy; however, when efficacy is comparable, patients appear to place greater weight on dosing frequency than on the duration of treatment administration, i.e., more frequent dosing appears to be less preferable to patients than longer administration/infusion time.  (more…)
Author Interviews, Cancer Research, Hematology / 03.12.2018

MedicalResearch.com Interview with: Maria-Victoria Mateos, MD, PhD Associate Professor of Medicine University of Salamanca Salamanca, Spain MedicalResearch.com: What is the background for this study? What are the main findings? Response: Alcyone trial is a phase 3 trial in which Daratumumab, the CD38 mAb has been added to a standard of care for elderly newly diagnosed myeloma patients, VMP, and compared with VMP. The main finding is that the addition of dara to VMP resulted into a significant benefit in PFS with a 57% reduction in the risk of progression and/or death. In addition, the benefit was also reported in terms of ORR and CR rate and 45% of patients receiving Dara VMP achieved CR. Minimal residual disease was evaluated and was undetectable in 27% of the patients what it is relevant because a 5% increase was observed in comparison with the publication one year ago. This means that Daratumumab as maintenance after the first 9 cycles daraVMP was able to upgrade the quality of response. Toxicity profile was acceptable and no new safety signals were reported. (more…)
Author Interviews, Cancer Research, Hematology, J&J-Janssen / 02.12.2018

MedicalResearch.com Interview with: Peter Voorhees, MD Plasma Cell Disorders Program Department of Hematologic Oncology and Blood Disorders Levine Cancer Institute Atrium Health MedicalResearch.com: What is the background for this study? Response: All multiple myeloma arises from its precursor conditions, monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM). Although the rate of progression to multiple myeloma for patients with MGUS is low (~5% over 5 years), patients with SMM have a ~50% likelihood of requiring therapy for their multiple myeloma within the first 5 years of diagnosis. For those at intermediate to high risk of disease progression, early intervention to delay progression of disease, thereby averting disease-related morbidities related and potentially changing the natural course of the disease, is highly desirable. On the other hand, given the fact that these patients are by definition asymptomatic and would otherwise be monitored off treatment, it is critical that any intervention applied in this group of patients is well tolerated. Daratumumab is a highly attractive candidate in this particular space, because it has single agent activity in heavily-pretreated relapsed/refractory multiple myeloma and a favorable side effect profile relative to many other myeloma therapeutics. Additionally, given the importance of impaired immune surveillance in multiple myeloma, the immuno-stimulatory effects of daratumumab in the bone marrow microenvironment could potentially reawaken robust T cell responses to the disease. (more…)
Author Interviews, Cancer Research, JAMA / 26.11.2018

MedicalResearch.com Interview with: Ola Landgren, MD, PhD Professor of Medicine Chief, Myeloma Service Department of Medicine Memorial Sloan Kettering Cancer Center New York, NY 10065 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Meta-analysis show that minimal residual disease (MRD) negativity is a strong predictor of longer progression-free survival (PFS). Emerging data show that an increasing proportion of newly diagnosed multiple myeloma patients obtain MRD negativity after modern combination therapy, even in the absence of bone marrow transplant. The first generation of 3-drug combination therapy (RVd) was associated with quite high rates of peripheral neuropathy which may be life-long. The current study was designed to define the rates of peripheral neuropathy in newly diagnosed multiple myeloma treated with the second generation of 3-drug combination therapy (KRd), and per default delayed transplant (i.e. collection of stem cells which were stored for potential future use). This single arm, phase 2 study found no cases of grade 3 peripheral neuropathy. The rates of MRD negativity wereunprecedented; 28 of 45 patients achieved MRD-negative CR (62%). The durability of MRD-negative CR has been observed up to 70 months (median duration 52.4 months). Patients who achieved MRD negativity by the end of cycle 8 had a 78% reduced risk of progression. The results were regardless of age or cytogenetic risk category. The results from this second generation of 3-drug combination therapy (KRd) without transplant,  compare favorably to first generation of 3-drug combination therapy (RVd) followed by stem cell transplant. (more…)
Author Interviews, Leukemia / 11.09.2018

MedicalResearch.com Interview with: Hans van Eenennaam, Ph.D. Executive vice president antibody research and site head Aduro Biotech Europe MedicalResearch.com: What is the background for this study? Response: A PRoliferation Inducing Ligand (APRIL) is a member of the tumor necrosis factor superfamily and has been shown to stimulate the proliferation and survival of healthy B-lymphocytes. Malignant B-lymphocytes, such as multiple myeloma, use APRIL primarily in the bone marrow to support its proliferation and survival. Studies have shown that APRIL is overproduced in patients with multiple myeloma and mediates primarily via binding to B-cell maturation antigen (BCMA) to stimulate a wide variety of responses that promote multiple myeloma growth and survival, as well as suppressing the immune system so that the tumor cells are protected and sustained in the bone marrow and can escape current available treatments. (more…)
ASCO, Author Interviews, Cancer Research, Hematology / 05.06.2018

MedicalResearch.com Interview with: PharmaMarDr. Javier Gómez García Senior Manager. Biostatistics and Data Management PharmaMar Madrid Area, Spain MedicalResearch.com: What is the background for this study? What are the main findings? Response: Multiple myeloma accounts for approximately 1 percent of all cancers and slightly more than 10 percent of all hematologic malignancies. At present, more than 80,000 new cases are reported worldwide each year, and the disease prevalence is increasing. Plitidepsin is a synthetic cyclic depsipeptide isolated from the marine tunicate Aplidium albicans targeting the proto-oncogene eEF1A2, which is over-expressed in multiple myeloma cells. In ADMYRE trial 255 relapsed and refractory multiple myeloma patients with at least three but not more than six prior regimens, including at least bortezomib and lenalidomide/thalidomide, were randomized at 2:1 ratio to receive plitidepsin 5 mg/m2 D1 and 15 plus DXM 40 mg D1, 8, 15 and 22 (P+DXM), or DXM 40 mg D1,8,15 and 22 (DXM) every four weeks. P+DXM met the primary endpoint, progression-free survival (PFS) assessed by an Independent Review Committee, showing a 35% risk reduction in the probability of progression or death. Indeed, a 20% risk reduction in the probability of death was also observed in spite of the fact that 44% of patients from control arm (DXM) switched to P+DXM arm after progression. Therefore, survival in the control arm might have been extended by the effect of plitidepsin, increasing the post progression survival and overestimating the survival observed in the control arm and consequently underestimating the actual difference between treatment arms. Several methods were used to assess the impact of crossover and the robustness of the results even when penalizations were applied; PharmaMar believes that strong evidence in terms of survival benefit in favour of P+DXM has been established.  (more…)
Author Interviews, Global Health, JAMA, Leukemia / 21.05.2018

MedicalResearch.com Interview with: Andrew J. Cowan, MD Seattle Cancer Care Alliance Division of Medical Oncology University of Washington, Seattle MedicalResearch.com: What is the background for this study? What are the main findings?   Response: Multiple myeloma (MM) is a plasma cell neoplasm with substantial morbidity and mortality. A comprehensive description of the global burden of multiple myeloma is needed to help direct health policy, resource allocation, research, and patient care. Myeloma cases and deaths increased from 1990 to 2016, with middle-income countries contributing the most to this increase. Treatment availability is very limited in countries with low socioeconomic development. (more…)
Author Interviews, Cancer Research, J&J-Janssen, Leukemia / 17.05.2018

MedicalResearch.com Interview with: Andrzej Jakubowiak, MD, PhD Professor of Medicine Director, Myeloma Program University of Chicago MedicalResearch.com: What is the background for this announcement? Would you briefly explain what is meant by multiple myeloma?   Response: DARZALEX (daratumumab) in combination with VELCADE (bortezomib), melphalan and prednisone - VMP - received U.S. FDA approval for the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant (ASCT). With this most recent approval, DARZALEX is now the first monoclonal antibody approved for newly diagnosed patients with this disease. Multiple myeloma is an incurable blood cancer that occurs when malignant plasma cells grow uncontrollably in the bone marrow. Despite the introduction of new medicines over the last decade, which has led to significant improvements in outcomes for patients with multiple myeloma, multiple myeloma remains an incurable disease. In 2018, it is estimated that 30,700 people will be diagnosed and 12,770 will die from the disease in the United States. (more…)
Author Interviews, Cancer Research, Chemotherapy, Journal Clinical Oncology / 06.02.2018

MedicalResearch.com Interview with: David S. Siegel, MD, PhD Chief, Myeloma Division John Theurer Cancer Center Hackensack University Medical Center Hackensack, NJ 07601 MedicalResearch.com: What is the background for this study? What are the main findings?
  •  We reported results from the prospectively planned final analysis of overall survival (OS) from the Phase 3 ASPIRE trial, an international, randomized study evaluating KYPROLIS (carfilzomib) in combination with lenalidomide and dexamethasone (KRd) versus lenalidomide and dexamethasone alone (Rd) in patients with relapsed or refractory multiple myeloma following treatment with one to three prior regimens. Overall survival was a secondary endpoint in the trial.
  • Data published last week in the Journal of Clinical Oncology demonstrated that the addition of KYPROLIS to Rd reduced the risk of death by 21 percent versus Rd alone and extended OS by 7.9 months (median OS 48.3 months for KRd versus 40.4 months for Rd, HR = 0.79, 95 percent CI, 0.67 – 0.95; one-sided p=0.0045).
  • Notably, an OS improvement of 11.4 months was observed for patients at first relapse (47.3 versus 35.9 months [HR = 0.81, 95 percent CI, 0.62 – 1.06]), supporting early use of KRd.
  • The safety data from ASPIRE was consistent with the known safety profile of KYPROLIS. The most common adverse events (greater than or equal to 20 percent) in the KYPROLIS arm were diarrhea, anemia, neutropenia, fatigue, upper respiratory tract infection, pyrexia, cough, hypokalemia, thrombocytopenia, muscle spasms, pneumonia, nasopharyngitis, nausea, constipation, insomnia and bronchitis.
Author Interviews, Cancer Research, Hematology / 21.12.2017

MedicalResearch.com Interview with: janseen-oncologyMaria-Victoria Mateos, MD, PhD University Hospital of Salamanca/IBSAL Salamanca, Spain MedicalResearch.com: What is the background for this study? What are the main findings? Response: The Phase 3 ALCYONE study data showed DARZALEX (daratumumab) in combination with bortezomib, melphalan, and prednisone (VMP) significantly improved clinical outcomes, including reducing the risk of disease progression or death by 50 percent, in newly diagnosed patients with multiple myeloma who are ineligible for autologous stem cell transplantation (ASCT) at a median follow-up of 16.5 months (Hazard Ratio [HR] = 0.50; 95 percent CI [0.38-0.65], p<0.0001). The median progression-free survival (PFS) for DARZALEX-VMP had not yet been reached, compared to an estimated median PFS of 18.1 months for patients who received VMP alone. In addition to reducing the risk of disease progression or death, DARZALEX significantly improved the overall response rate (ORR) as compared to VMP alone, including more than doubling rates of stringent complete response, significantly improved rates of very good partial response or better and complete response or better (CR). The most common (≥10 percent) Grade 3/4 treatment-emergent adverse events (TEAEs) for DARZALEX-VMP vs. VMP were neutropenia (40 percent vs. 39 percent), thrombocytopenia (34 percent vs. 38 percent), anemia (16 percent vs. 20 percent) and pneumonia (11 percent vs. 4 percent). One patient in each arm discontinued treatment due to pneumonia, and 0.9 percent of patients discontinued DARZALEX due to an infection. Twenty-eight percent of patients experienced infusion reactions (IRs) due to DARZALEX.. In the DARZALEX-VMP arm, 42 percent of patients experienced a serious adverse event (SAE), compared to 33 percent in the VMP arm. The study findings were as a late-breaking abstract (Abstract #LBA-4) at the 59th American Society of Hematology (ASH) Annual Meeting in Atlanta, and simultaneously published in the New England Journal of Medicine (NEJM). (more…)
Author Interviews, Hematology / 13.12.2017

MedicalResearch.com Interview with: Craig CHofmeisterMD, MPH The Ohio State University  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Preliminary data presented from the randomized, open-label, Phase 2 CENTAURUS (SMM2001) study evaluated three dosing schedules for DARZALEX monotherapy in patients with intermediate or high-risk smoldering multiple myeloma. A total of 123 patients were enrolled, with a median time since initial smoldering multiple myeloma diagnosis of 6.83 months (0.4-56). Patients were randomized to one of three treatment arms receiving DARZALEX 16 mg/kg intravenously in 8-week cycles: 1.) a long-intense dosing schedule (LONG) where DARZALEX was administered weekly in Cycle 1, every other week in Cycle 2-3, every 4 weeks in Cycle 4-7, and every 8 weeks up to Cycle 20; 2.) an intermediate dosing schedule (INT), where DARZALEX was given weekly for 1 cycle, and every 8 weeks up to Cycle 20 and; 3.) a short intense dosing schedule (SHORT), where DARZALEX was given weekly for 1 cycle. Results from the study showed DARZALEX monotherapy had a tolerable safety profile in patients with intermediate or high-risk smoldering multiple myeloma, with the most common treatment-emergent adverse events (TEAEs) being fatigue, cough, headache and insomnia. The efficacy endpoints included overall response rate, progression free survival, time to next treatment, and overall survival rate at 4 years. These study results serve as the basis for a Phase 3 study for DARZALEX in smoldering multiple myeloma, which is actively enrolling. These findings demonstrated DARZALEX had a manageable safety profile in patients with intermediate or high-risk smoldering multiple myeloma. (more…)
Author Interviews, Leukemia, Race/Ethnic Diversity, Social Issues / 22.08.2016

MedicalResearch.com Interview with: Luciano J. Costa, MD, PhD Associate Professor Department of Medicine and UAB-CCC Bone Marrow Transplantation and Cell Therapy Program Birmingham, AL 35294 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Even though expected survival for multiple myeloma patients has increased over the last two decades, that improvement has not been much more pronounced among White than among patients of racial/ethnic minorities. It is possible that such discrepancy results from unequal access to care, particularly as treatment becomes more complex and expensive. We used a large dataset of patients with  multiple myeloma to explore how socioeconomic factors, specifically marital status, income and insurance affect outcome and how these factors relate to race/ethnicity. (more…)
ASCO, Author Interviews, Cancer Research, Stem Cells / 05.06.2016

MedicalResearch.com Interview with: Philip McCarthy, BA, MD Professor of Oncology Director, Blood and Marrow Transplant Program Roswell Park Cancer Institute Associate Professor of Medicine Jacobs School of Medicine and Biomedical Sciences State University of New York at Buffalo Buffalo, NY 14263 MedicalResearch.com: What is the background for this study? What are the main findings? Dr. McCarthy: There have been three Phase III studies that examined the role of maintenance lenalidomide after autologous stem cell transplant (ASCT) for newly diagnosed multiple myeloma patients. IFM 2005-02 (France), CALGB 100104 (Alliance, USA), GIMEMA-RVMM-PI-209 (Italy). All three studies had progression free survival (PFS) as their primary endpoint and all demonstrated a superior PFS when compared to placebo or no therapy after ASCT. However only the CALGB 100104 study demonstrated a statistically superior overall survival (OS). Thus, a meta-analysis was necessary to assess the effect of post-ASCT lenalidomide maintenance on overall survival. This study utilized a pooled analysis of updated primary-source patient data from all three studies after the primary efficacy analyses had been conducted. The meta-analysis demonstrated that there is a statistically superior OS (P value=0.001, HR=0.74 (0.62-0.89)), Median OS for no maintenance or placebo was 86 months and the median OS for lenalidomide had not been reached. The median OS for lenalidomide treatment arm was extrapolated to be 116 months based on median of the control arm and HR (median, 86 months; HR = 0.74). Thus, there is a 26% reduction in the risk of death which is an estimated 2.5 year increase in median OS. There is an increased incidence of second primary malignancies with lenalidomide maintenance when compared to placebo but this risk is less than the risk of dying when not receiving lenalidomide. (more…)
Author Interviews, Cancer Research, JAMA / 09.03.2015

Prof. Sigurdur Y Kristinsson Professor of Hematology University of IcelandMedicalResearch.com Interview with: Prof. Sigurdur Y Kristinsson Professor of Hematology University of Iceland MedicalResearch: What is the background for this study? What are the main findings? Prof. Kristinsson: Multiple myeloma is always preceded by a precursor condition called monoclonal gammopathy of undetermined significance (MGUS). MGUS is characterized by a detectable monoclonal protein in persons without evidence for end-organ damage or other related plasma cell or lymphoproliferative disorders. MGUS is very common and is detected in approximately 5 percent of persons 70 years or older. However, only a small proportion of MGUS progresses to a malignant disorder, in fact the annual risk of progression to multiple myeloma or other related disorders is on average 1 percent, with varying risks according to risk groups. Current guidelines suggest, depending on the individual patient’s clinical risk score, life-long monitoring of MGUS individuals to detect progression to multiple myeloma or related disorders. At this time, the impact of annual monitoring on the outcome of patients who eventually develop multiple myeloma is unclear. Using high-quality population-based data from Sweden, we estimated the impact of prior knowledge of MGUS diagnosis and comorbidities on multiple myeloma survival, by performing a large population-based study using data on more than 14,000 multiple myeloma patients diagnosed in Sweden 1976-2005, with follow-up through 2007. The hypothesis that detection and follow-up of MGUS may influence survival in multiple myeloma is unlikely to ever be tested in a prospective clinical study due to the large sample size required with long follow-up time, and consequent extreme costs. We found that multiple myeloma patients with prior knowledge of MGUS had significantly 15% better survival, despite having significantly more comorbidities. Interestingly, low-risk MGUS (with very low M-protein) had highest risk of death. The observation that low M-protein concentration at MGUS diagnosis was associated with poorer multiple myeloma survival may reflect less frequent clinical follow-up. Our observations stress the importance of clinical follow-up in MGUS, regardless of risk stratification. (more…)
Author Interviews, Cancer Research / 11.02.2015

MedicalResearch.com Interview with: Dr. Dixie-Lee Esseltine MD, FRCPC Vice President, Oncology Clinical Research Takeda. MedicalResearch: What is Ixazomib? Dr. Dixie-Lee Esseltine: Ixazomib is an investigational, oral, once-weekly proteasome inhibitor (PI) that is being investigated in multiple Phase 3 trials in multiple myeloma (MM) and systemic light-chain (AL) amyloidosis. It is the first oral  proteasome inhibitor to enter Phase 3 clinical trials. Proteasome inhibition is a mechanism underpinning an established standard of care in the treatment of multiple myeloma. However, the current biweekly parenteral administration of proteasome inhibitors may pose challenges to patients. The ability to demonstrate that an oral, once-weekly PI can extend PFS would be a remarkably important finding in the effort to address these challenges. Early studies suggest ixazomib, has activity in MM patients, both as a single agent in relapsed patients and in combination in frontline patients. Ixazomib was granted orphan drug designation in multiple myeloma in both the U.S. and Europe in 2011, and for AL amyloidosis in both the U.S. and Europe in 2012. It was granted Breakthrough Therapy Designation for AL amyloidosis in the U.S. in 2014. MedicalResearch: What is the design for this study? Dr. Dixie-Lee Esseltine: The TOURMALINE MM-1 study (C16010) is a phase 3, randomized, double-blind study comparing ixazomib plus lenalidomide and dexamethasone versus placebo plus lenalidomide and dexamethasone in patients with relapsed and/or refractory multiple myeloma. Patients were randomized to receive ixazomib 4.0mg days 1,8 and 15 or placebo with  lenalidomide 25mg days 1-21 and dexamethasone 40mg days 1,8,15 and 22. Treatment was given every 28 days until disease progression or unacceptable toxicity. Evaluation was based on the International Myeloma Working Group (IMWG) Uniform Response Criteria. (more…)