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Background On the basis of the DREAMM‐2 study (ClinicalTrials.gov identifier NCT03525678), single‐agent belantamab mafodotin (belamaf) was approved for patients with relapsed or refractory multiple myeloma (RRMM) who received ≥4 prior therapies, including anti‐CD38 therapy. The authors investigated longer term efficacy and safety outcomes in DREAMM‐2 after 13 months of follow‐up among patients who received belamaf 2.5 mg/kg. Methods DREAMM‐2 is an ongoing, phase 2, open‐label, 2‐arm study investigating belamaf (2.5 or 3.4 mg/kg) in patients with RRMM who had disease progression after ≥3 lines of therapy and were refractory to immunomodulatory drugs and proteasome inhibitors and refractory and/or intolerant to an anti‐CD38 therapy. The primary outcome was the proportion of patients that achieved an overall response, assessed by an independent review committee. Results As of January 31, 2020, 10% of patients still received belamaf 2.5 mg/kg. Thirty‐one of 97 patients (32%; 97.5% confidence interval [CI], 21.7%‐43.6%) achieved an overall response, and 18 responders achieved a very good partial response or better. Median estimated duration of response, overall survival, and progression‐free survival were 11.0 months (95% CI, 4.2 months to not reached), 13.7 months (95% CI, 9.9 months to not reached), and 2.8 months (95% CI, 1.6‐3.6 months), respectively. Response and survival outcomes in patients who had high‐risk cytogenetics or renal impairment were consistent with outcomes in the overall population. Outcomes were poorer in patients with extramedullary disease. In patients who had a clinical response and prolonged dose delays (>63 days; mainly because of corneal events), 88% maintained or deepened responses during their first prolonged dose delay. Overall, there were no new safety signals during this follow‐up. Conclusions Extended follow‐up confirms sustained clinical activity without new safety signals with belamaf in this heavily pretreated patient population with RRMM., Extended follow‐up of patients enrolled in the ongoing phase 2 DREAMM‐2 study confirms sustained clinical activity without new safety signals in patients with relapsed or refractory multiple myeloma who receive belantamab mafodotin 2.5 mg/kg every 3 weeks. These data show that belantamab mafodotin has the potential to shift the treatment paradigm in this heavily pretreated, anti‐CD38 monoclonal antibody–exposed patient population, which has a poor prognosis and few alternative treatment options.

Background Racial disparity in the incidence of multiple myeloma is well established; however, to the authors' knowledge, little is known regarding the impact of racial differences on disease characteristics, response to therapy, and clinical outcome. Methods The authors studied 453 patients (174 of whom were black and 279 of whom were white) who underwent transplant between 2000 and 2013. The median follow-up was 4.4 years. Results Black patients were significantly younger than white patients (median age, 54 years vs 59 years; P

BACKGROUND. Bortezomib is active in heavily pretreated multiple myeloma patients; the dose-limiting toxicity is peripheral neuropathy (PN). METHODS. The authors retrospectively reviewed the incidence, severity, and risk factors for PN in 78 patients who received bortezomib. The median age was 57 years (range, 33–80 years), 62% of patients were men, and 37% of patients were African Americans. Seventeen patients (22%) had diabetes mellitus (DM), and 66 patients (85%) had received thalidomide. Before bortezomib treatment, 37% of the patients reported subjective, grade 1 or 2 PN. Patients received bortezomib alone (n = 10 patients) plus dexamethasone (n = 36 patients) and thalidomide (n = 20 patients) or chemotherapy (n = 12 patients). PN affected 52% of patients, including grade 3 and 4 PN in 15% and 7%, respectively. RESULTS. Twelve patients stopped bortezomib because of side effects that included PN (n = 9 patients), diarrhea (n = 2 patients) and cytomegalovirus pneumonia (n = 1 patient); 11 patients had dose reductions because of PN. Grade 4 PN affected 6 patients (sensory, n = 4 patients; motor/sensory, n = 2 patients). The onset of grade 4 PN was sudden rather than cumulative. Factors that were predictive of PN grade were baseline PN (P = .002), prior thalidomide use (P = .03), and the presence of DM (P = .03). Multiple myeloma responses included complete, near complete, and partial responses in 5% of patients, 10% of patients, and 27% of patients, respectively. Responses were independent of PN and of whether bortezomib was combined with chemotherapy or thalidomide. Patients remained on therapy longer for a median of 5 cycles (range, 2–36 cycles) when they received bortezomib plus thalidomide versus 3 cycles (range, 1–19 cycles) for the other combinations. PN therapy was mostly supportive. It was noteworthy that 6 of 9 patients with PN who received lenalidomide as salvage therapy after bortezomib had significant improvement in their symptoms. CONCLUSIONS. The risk of bortezomib-related PN was greater in patients who had PN and DM at baseline. The authors concluded that an unexpected, symptomatic improvement of PN on lenalidomide is worth further investigation. Cancer 2007. © 2007 American Cancer Society.

Racial disparity in the incidence of multiple myeloma is well established; however, to the authors' knowledge, little is known regarding the impact of racial differences on disease characteristics, response to therapy, and clinical outcome.The authors studied 453 patients (174 of whom were black and 279 of whom were white) who underwent transplant between 2000 and 2013. The median follow-up was 4.4 years.Black patients were significantly younger than white patients (median age, 54 years vs 59 years; P.0001), more frequently presented with anemia (P = .04), had more of the immunoglobulin G isotype (P.001), and had a borderline favorable cytogenetic risk (P = .06). Overall response to induction was similar, but deeper responses were observed in more white patients compared with black patients receiving immunomodulatory drug-based induction (P = .02). Referral for transplant was significantly delayed in black individuals (median, 1.3 years vs 0.9 years; P = .003). Overall survival from the time of transplant was similar for black and white patients, with medians of 6.2 years and 5.7 years, respectively, but survival from the time of diagnosis was significantly longer among black individuals (median, 7.7 years vs 6.1 years; P = .03). Maintenance therapy was found to positively impact progression-free survival but not overall survival, irrespective of race.The results of the current study confirm ethnic differences in age, referral patterns, response to therapy, and overall survival. Future validation of these disparities is urgently needed.

BACKGROUND Although various clinical observations suggested that myeloma cell growth might be modulated by the immune system, evidence supporting the in situ immunogenicity of myeloma cells remains scarce. The authors reasoned that if there is any specific T-cell/tumor cell interaction in myeloma, it is most likely reflected in the T-cell population in the vicinity of the tumor cells. METHODS The authors used a molecular method to compare the T-cell populations in the vicinity of tumor cells with those in the peripheral blood in patients with plasmacytomas and multiple myeloma. RESULTS Six patients were studied. When compared with the peripheral blood from the corresponding patients, T cells in the vicinity of tumor cells in five of the six patients showed significant contraction of the T-cell receptor (TCR) Vβ repertoire. In addition to this, the T cells isolated from the sites of the tumor cells from four of these five patients also demonstrated significant increase in the number of TCR Vβ gene families with restricted number of CDR3 size peaks and loss of the normal CDR3 size gaussian distribution pattern. These findings were observed in patients who experienced recurrence after allogeneic stem cell transplantation and also in those who had autologous stem cell transplant. They also were found in previously untreated myeloma patients. In all six patients, distinct TCR Vβ recurring transcripts indicative of a T-cell clonal expansion were found in the vicinity of the tumor cells and either absent or detected at only a low frequency in the peripheral blood. CONCLUSIONS Our results provide evidence for an in situ local T-cell clonal expansion in the vicinity of tumor cells and support the presence of specific T-cell/tumor cell interaction in myeloma. Cancer 2001;91:900–8. © 2001 American Cancer Society.