Author Interviews, Cancer Research, JAMA / 26.11.2018
Second Generation 3-Drug Combination Found Safe & Effective for Newly Diagnosed Multiple Myeloma
MedicalResearch.com Interview with:
[caption id="attachment_46183" align="alignleft" width="200"] Dr. Landgren[/caption]
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.
Dr. Landgren[/caption]
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.
Dr. Mangione[/caption]
Dr. Carol Mangione M.D., M.S.P.H., F.A.C.P
Ronald Reagan UCLA Medical Center
Division Chief of General Internal Medicine and Health Services Research
Professor of Medicine.
Barbara A. Levey, MD, and Gerald S. Levey, MD
Endowed chair in medicine David Geffen School of Medicine
University of California
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Unhealthy alcohol use is relatively common and is increasing among U.S. adults. Alcohol use is the third leading cause of preventable death in the U.S. and contributes to more than 88,000 deaths per year. In pregnancy, it also leads to birth defects and developmental problems in children. The Task Force found that screening tests and brief counseling interventions can help detect and reduce unhealthy alcohol use among adults, and in turn help prevent negative consequences related to alcohol use. For adolescents ages 12 to 17, clinicians should use their best judgment when deciding whether or not to screen and refer their patients to counseling, until we have better studies available.
Cara Tannenbaum, MD, MSc
Director | Directrice
Canadian Deprescribing Network
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The D-Prescribe trial was driven by the need to show that seniors can cut down on their medication in a safe and effective manner. Pharmacists intervened in a proactive way to flag patients who were on potentially risky meds such as sleeping pills, NSAIDs and glyburide and to inform them of the risks, using an educational brochure. Pharmacists also communicated with their physician using an evidence-based pharmaceutical opinion to spark conversations about deprescribing. As a result, 43% of patients succeeded in discontinuing at least one medication over the next 6 months.
Dr. Ray[/caption]
Joel Ray MD, MSc, FRCPC
Institute of Health Policy, Management and Evaluation
Faculty of Medicine
University of Toronto, Toronto
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Many women who die within childbirth or soon thereafter experience rapid onset of morbidity/illness before succumbing. Thus, severe maternal morbidity (SMM) offers a detectable (or set of detectable) conditions that might be dealt with before they progress to a fatality. Even so, severe maternal morbidity alone can be non-fatal, but create disability for a new mother (e.g., a stroke), or prolong separation of mother and newborn.
So, we showed that, as the number of severe maternal morbidity indicators rises, so does the probability of maternal death. This relation was exponential in nature. 
Nicholas Reed AuD[/caption]
Nicholas S. Reed, AuD
Assistant Professor | Department of Otolaryngology-Head/Neck Surgery
Core Faculty | Cochlear Center for Hearing and Public Health
Johns Hopkins University School of Medicine
Johns Hopkins University Bloomberg School of Public Health
MedicalResearch.com: What is the background for this study?
Response: This study was a true team effort. It was funded by AARP and AARP Services, INC and the research was a collaboration of representatives from Johns Hopkins University, OptumLabs, University of California – San Francisco, and AARP Services, INC. Given all of the resent research on downstream effects of hearing loss on important health outcomes such as cognitive decline, falls, and dementia, the aim was to explore how persons with hearing loss interacted with the healthcare system in terms of cost and utilization.
MedicalResearch.com: What are the main findings?
Response: Over a 10 year period, untreated hearing loss (hearing aid users were excluded from this study as they are difficult to capture in the claims database) was associated with higher healthcare spending and utilization. Specifically, over 10 years, persons with untreated hearing loss spent 46.5% more, on average, on healthcare (to the tune of approximately $22000 more) than those without evidence of hearing loss. Furthermore, persons with untreated hearing loss had 44% and 17% higher risk for 30-day readmission and emergency department visit, respectively.
Similar relationships were seen across other measures where persons with untreated hearing loss were more likely to be hospitalized and spent longer in the hospital compared to those without evidence of hearing loss. 
Dr. Yano[/caption]
Yuichiro Yano MD PhD
Assistant Professor in Community and Family Medicine
Duke University
MedicalResearch.com: What is the background for this study?
Response: New blood pressure guidelines, issued in 2017 in the US, lowered the blood pressure thresholds for hypertension from systolic blood pressure/diastolic ≥140/90 mm Hg to systolic/diastolic ≥130/80 mm Hg. This change increased the prevalence of hypertension two- to three-fold among young adults. The guidelines also newly defined elevated blood pressure as, 120-129 mmHg systolic blood pressure over 80 mmHg diastolic or less. However, no study investigated that high blood pressure, as defined by the new criteria, is something that younger people should be concerned about as a potential precursor to serious problems.
Our study is among the first to report that people younger than age 40 who have elevated blood pressure or hypertension are at increased risk of heart failure, strokes and blood vessel blockages as they age.