Vincent Rajkumar

In this phase 1/2 study, carfilzomib was added to high-dose melphalan conditioning prior to autologous stem cell transplantation (ASCT) in patients with multiple myeloma that had been treated with ≤2 prior lines of therapy. Carfilzomib was escalated at doses of 27, 36, 45, and 56 mg/m2 on days -6, -5, -2, and -1 before ASCT in the phase 1 component of the study. In addition, all the patients received melphalan 100 mg/m2 on days -4 and -3. The primary endpoint of the phase 1 component was to identify the maximum tolerated dose, and the primary endpoint of the phase 2 component was the rates of complete response (≥CR) at 1 year after ASCT...

Patients with multiple myeloma (MM) that do not respond to initial therapy have worse outcomes compared to primary responders, and effective treatments are lacking in this population. However, the outcomes of primary refractory disease in the modern treatment era have not been studied. We reviewed MM patients treated with triplet/quadruplet therapy in our institution to assess the incidence of primary refractory disease and the impact of salvage therapies in this population. We identified 1127 patients, of which 1086 were evaluated for hematologic response after 4-6 cycles...

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BACKGROUND: Multiple laboratory tests are employed for detection of monoclonal proteins in patients and include serum protein electrophoresis (SPEP), immunofixation electrophoresis, free light chain (FLC) immunoassay, and mass spectrometry (Mass-Fix). Recently, reports on a drift in FLC quantitation results have been brought to light. METHODS: We studied a cohort of 16 887 patients whose sera were tested for a monoclonal protein by a FLC assay, serum protein electrophoresis, and Mass-Fix...

Overall survival estimates from diagnosis are valuable for guiding treatment, but do not consider the years already survived. Conditional survival (CS) provides dynamic survival predictions over time. This study was conducted to estimate CS at 1-8 years from diagnosis and the impact of baseline prognostic factors on CS in multiple myeloma (MM) patients. This is a retrospective study including 2556 MM patients diagnosed between 2004 and 2019. CS (t | s) was defined as the probability of surviving t years given survival of s years...

BACKGROUND: The TOURMALINE-MM4 trial demonstrated a significant and clinically meaningful progression-free survival (PFS) benefit with ixazomib versus placebo as postinduction maintenance in nontransplant, newly-diagnosed multiple myeloma patients, with a manageable and well-tolerated toxicity profile. MATERIALS AND METHODS: In this subgroup analysis, efficacy and safety were assessed by age (< 65, 65-74, and ≥ 75 years) and frailty status (fit, intermediate-fit, and frail)...

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Light chain cast nephropathy (LCCN) is a leading cause of acute kidney injury (AKI) in patients with multiple myeloma (MM) and is now defined as a myeloma defining event. While the long-term prognosis has improved with novel agents, short-term mortality remains significantly higher in patients with LCCN especially if the renal failure is not reversed. Recovery of renal function requires a rapid and significant reduction of the involved serum free light chain. Therefore, proper treatment of these patients is of the utmost importance...

Monoclonal gammopathy of undetermined significance (MGUS) is a benign hematological condition with the potential to progress to malignant conditions including multiple myeloma and Waldenstrom macroglobulinemia. Medications that modify progression risk have yet to be identified. To investigate, we leveraged machine-learning and electronic health record (EHR) data to screen for drug repurposing candidates. We extracted clinical and laboratory data from a manually curated MGUS database, containing 16,752 MGUS patients diagnosed from January 1, 2000 through December 31, 2021, prospectively maintained at Mayo Clinic...

Some cytogenetic abnormalities (CAs) are associated with poorer prognosis in multiple myeloma (MM); proteasome inhibitors appear to benefit patients with high-risk CAs. We evaluated 2247 MM patients from the TOURMALINE-MM1/-MM2/-MM3/-MM4 trials to assess the PFS benefit of ixazomib plus lenalidomide-dexamethasone (Rd) vs placebo-Rd (TOURMALINE-MM1/-MM2) or ixazomib vs placebo (TOURMALINE-MM3/-MM4) in specific high-risk CAs. After a pooled median follow-up of 25.6 months, the hazard ratio (HR) for PFS with ixazomib- vs placebo-based therapy for high-risk patients was 0...

Lenalidomide-containing (R) triplet and quadruplet regimens are the standard of care for multiple myeloma (MM) and have been shown to increase the risk of thrombosis. The association between thromboembolism (TE) and survival in the novel multidrug era is not yet delineated. In this study, we evaluated the incidence of TE during the first year of MM diagnosis, its association with the type of induction regimen, and its impact on overall survival. We studied 672 newly diagnosed MM (NDMM) patients who received a triplet or quadruplet lenalidomide-based induction at the Mayo Clinic, Rochester...

Waldenström macroglobulinemia (WM) is a rare, indolent lymphoma, that predominately affects the elderly. We report the outcomes of young WM patients, evaluated over five decades, compared to their older counterparts, matched for the time of diagnosis. Between January 1, 1960 and October 31, 2013, 140 (11.8%) WM patients were ≤50 years of age at diagnosis in our database, and their estimated 10-year overall survival (OS) was 74%, with death attributable to WM in a higher proportion of patients compared to their older (≥65 years) counterparts (91% vs...

INTRODUCTION: The current treatment paradigm of AL amyloidosis lacks effective fibril-directed therapies. Doxycycline has been shown to have anti-fibril properties in preclinical models. In 2012, we reported that posttransplant prophylaxis with doxycycline was associated with improved survival compared to penicillin in patients with haematologic response. We provide here updated results after long-term follow up. METHODS: We included 553 patients who underwent transplant between July 24th , 1996, and June 24th , 2014...

Monoclonal gammopathy of undetermined significance (MGUS) is of considerable clinical importance to primary care physicians given its high prevalence in the general population. MGUS has a variable but lifelong risk for progression to hematologic cancer, such as multiple myeloma, Waldenström macroglobulinemia, or light-chain amyloidosis. In addition, MGUS has been associated with several nonmalignant yet symptomatic disorders that require therapy directed toward eliminating the monoclonal gammopathy. Thus, it is important not only to understand the essentials of diagnosing and monitoring patients with MGUS but also to recognize when to refer patients with MGUS to a specialist...

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The treatment landscape for relapsed multiple myeloma (MM) has increased. In this study, we aimed to characterize 2nd (n = 1439) and 3rd (n = 1104) line regimens and compare the results between subgroups based on the year of treatment initiation (2nd line: 2003-2008, 2009-2015, 2016-2021; 3rd line: 2004-2009, 2010-2015, and 2016-2021). In both the second- and third- lines, we observed increasing use of novel agents (from 78 to 95% and from 77 to 95%, respectively) and triplet regimens (from 15 to 69% and from 21 to 71%, respectively)...

BACKGROUND: Sarcopenia increases with age and is associated with poor survival outcomes in patients with cancer. By using a deep learning-based segmentation approach, clinical computed tomography (CT) images of the abdomen of patients with newly diagnosed multiple myeloma (NDMM) were reviewed to determine whether the presence of sarcopenia had any prognostic value. METHODS: Sarcopenia was detected by accurate segmentation and measurement of the skeletal muscle components present at the level of the L3 vertebrae...

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Patients with multiple myeloma (MM) have a lower efficacy from COVID-19 vaccination and a high rate of mortality from COVID-19 in hospitalized patients. However, the overall rate and severity of COVID-19 infection in all settings (including non-hospitalized patients) and the independent impact of plasma cell-directed therapies on outcomes needs further study. We reviewed the medical records of 9,225 patients with MM or AL amyloidosis (AL) seen at Mayo Clinic Rochester, Arizona, and Florida between 12/01/2019 and 8/31/2021 and identified 187 patients with a COVID-19 infection (n=174 MM, n=13 AL)...