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Summary Background Pomalidomide and dexamethasone is a standard of care for patients with multiple myeloma in whom bortezomib and lenalidomide treatment has failed. KEYNOTE-183 assessed efficacy and safety of pomalidomide and dexamethasone with or without pembrolizumab in patients with relapsed or refractory multiple myeloma. Here, we present the findings of an unplanned, ad-hoc interim analysis at the request of the US Food and Drug Administration (FDA). Methods KEYNOTE-183 was a randomised, open-label, phase 3 trial done at 97 medical centres across 11 countries (Australia, Canada, France, Germany, Israel, Italy, Japan, New Zealand, Norway, Spain, and USA). Patients aged at least 18 years with multiple myeloma, an Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1, previously treated with at least two lines of therapy (excluding pomalidomide) and refractory to the last line were randomly assigned 1:1 to the pembrolizumab plus pomalidomide and dexamethasone group or the pomalidomide and dexamethasone group via an interactive voice response or integrated web response system. Patients received oral pomalidomide 4 mg daily on days 1–21 and oral low-dose dexamethasone 40 mg on days 1, 8, 15, and 22 in 28-day cycles, with or without intravenous pembrolizumab 200 mg every 3 weeks. The dual primary endpoints were progression-free survival and overall survival. Efficacy was assessed in all randomly assigned patients and safety was assessed in patients who received at least one dose of study treatment. The trial is registered at ClinicalTrials.gov , number NCT02576977 , and it is closed for accrual. Findings Between Jan 18, 2016, and June 7, 2017, 249 patients were randomly assigned to either the pembrolizumab plus pomalidomide and dexamethasone group (n=125) or the pomalidomide and dexamethasone group (n=124). On July 3, 2017, the FDA established that risks associated with the triple combination outweighed benefits and halted the study. Median follow-up was 8·1 months (IQR 4·5–10·9). Median progression-free survival was 5·6 months (95% CI 3·7–7·5) in the pembrolizumab plus pomalidomide and dexamethasone group versus 8·4 months (5·9–not reached) in the pomalidomide and dexamethasone group; progression-free survival estimates at 6 months were 48% (95% CI 37–58) versus 60% (49–69) at 6 months (hazard ratio [HR] 1·53; 95% CI 1·05–2·22; p=0·98). Median overall survival was not reached (95% CI 12·9–not reached) versus 15·2 months (12·7–not reached; HR 1·61; 95% CI 0·91–2·85; p=0·95); overall survival estimates at 6 months were 82% (95% CI 74–88) versus 90% (82–95). Serious adverse events occurred in 75 (63%) of 120 patients in the pembrolizumab plus pomalidomide and dexamethasone group versus 56 (46%) of 121 patients in the pomalidomide and dexamethasone group. Four (3%) treatment-related deaths occurred in the pembrolizumab plus pomalidomide and dexamethasone group (one each of unknown cause, neutropenic sepsis, myocarditis, and Stevens–Johnson syndrome); myocarditis and Stevens-Johnson syndrome were considered related to pembrolizumab. No treatment-related deaths were reported in the pomalidomide and dexamethasone group. Interpretation The results from this unplanned, FDA-requested, interim analysis showed that the benefit–risk profile of pembrolizumab plus pomalidomide and dexamethasone is unfavourable for patients with relapsed or refractory multiple myeloma. Funding Merck Sharp & Dohme, a subsidiary of Merck & Co (Kenilworth, NJ, USA).

Secretion of monoclonal immunoglobulins (MIg) detected in the serum and/or urine is one of the typical features of multiple myeloma (MM). However, some patients secrete MIg in quantities below “measurable” (termed oligosecretory MM) and others have no detectable MIgs by standard serum and urine immunofixation (termed non-secretory MM). In a cohort of 852 consecutive patients with active myeloma, we identified 100 (11.7%) patients with oligo/non-secretory MM, including 20 (2.3%) with non-secretory MM. Compared to patients with secretory MM, these were younger, less anemic, and had less often renal dysfunction and less extensive bone marrow infiltration. Presence and extent of bone disease were similar, however, hypercalcemia was less common and more often is ISS (International Staging System)-1 and, in those with available FISH (Fluoresense In Situ Hybridization) , high-risk cytogenetics were less common. FLCs (Free Light Chains) were available in 17 patients with non-secretory MM: only 3 had normal FLC ratio; the others had abnormal ratio and 9/14 had involved FLC ≥ 100 mg/L. The 4-year OS for patients with oligo/non-secretory disease was 64% vs 58% for secretory MM. In multivariate analysis, oligo/non-secretory disease was not an independent prognostic factor per se. Thus, 12% of MM patients present with oligo/non-secretory disease at diagnosis and have different biologic characteristics but similar outcome to other MM patients. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature.

We investigated incidence, characteristics and outcome of patients with macrofocal multiple myeloma (MFMM) treated mainly with novel therapies. Based on definition (BMPCs

Multiple myeloma (MM) remains an incurable disease, with little information available on its management in real-world clinical practice. The results of the present prospective, noninterventional observational study revealed great diversity in the treatment regimens used to treat MM. Our results also provide data to inform health economic, pharmacoepidemiologic, and outcomes research, providing a framework for the design of protocols to improve the outcomes of patients with MM. Background: The present prospective, multinational, noninterventional study aimed to document and describe real-world treatment regimens and disease progression in multiple myeloma (MM) patients. Patients and Methods: Adult patients initiating any new MM therapy from October 2010 to October 2012 were eligible. A multistage patient/site recruitment model was applied to minimize the selection bias; enrollment was stratified by country, region, and practice type. The patient medical and disease features, treatment history, and remission status were recorded at baseline, and prospective data on treatment, efficacy, and safety were collected electronically every 3 months. Results: A total of 2358 patients were enrolled. Of these patients, 775 and 1583 did and did not undergo stem cell transplantation (SCT) at any time during treatment, respectively. Of the patients in the SCT and non-SCT groups, 49%, 21%, 14%, and 15% and 57%, 20%, 12% and 10% were enrolled at treatment line 1, 2, 3, and ≥ 4, respectively. In the SCT and non-SCT groups, 45% and 54% of the patients had received bortezomib-based therapy without thalidomide/lenalidomide, 12% and 18% had received thalidomide/lenalidomide-based therapy without bortezomib, and 30% and 4% had received bortezomib plus thalidomide/lenalidomide-based therapy as frontline treatment, respectively. The corresponding proportions of SCT and non-SCT patients in lines 2, 3, and ≥ 4 were 45% and 37%, 30% and 37%, and 12% and 3%, 33% and 27%, 35% and 32%, and 8% and 2%, and 27% and 27%, 27% and 23%, and 6% and 4%, respectively. In the SCT and non-SCT patients, the overall response rate was 86% to 97% and 64% to 85% in line 1, 74% to 78% and 59% to 68% in line 2, 55% to 83% and 48% to 60% in line 3, and 49% to 65% and 36% and 45% in line 4, respectively, for regimens that included bortezomib and/or thalidomide/lenalidomide. Conclusion: The results of our prospective study have revealed great diversity in the treatment regimens used to manage MM in real-life practice. This diversity was linked to factors such as novel agent accessibility and evolving treatment recommendations. Our results provide insight into associated clinical benefits. © 2018 The Authors