5 research outputs found
Chimeric antigen receptor T-cell therapy for multiple myeloma: a consensus statement from The European Myeloma Network
Adoptive cellular therapy using chimeric antigen receptor T-cell (CART) therapy is currently being evaluated in patients with relapsed /
refractory multiple myeloma (MM). The majority of CAR-T cell programs now being tested in clinical trials are targeting B-cell maturation antigen. Several recent phase I / II trials show promising preliminary results in
patients with MM progressing on proteasome inhibitors, immunomodulatory drugs and monoclonal antibodies targeting CD38. CAR-T cell therapy
is a potentially life-threatening strategy that can only be administered in
experienced centers. For the moment, CAR-T cell therapy for MM is still
experimental, but once this strateg
Lenalidomide Maintenance with or without Prednisone in Newly Diagnosed Myeloma Patients: A Pooled Analysis
We conducted a pooled analysis of two phase III trials, RV-MM-EMN-441 and EMN01,
to compare maintenance with lenalidomide-prednisone vs. lenalidomide in newly diagnosed
transplant-eligible and -ineligible myeloma patients. Primary endpoints were progression-free survival, progression-free survival 2 and overall survival with both regimens. A secondary aim
was to evaluate the impact of duration of maintenance on overall survival and on outcome after
relapse. A total of 625 patients (lenalidomide-prednisone arm, n = 315; lenalidomide arm, n = 310)
were analyzed. The median follow-up was 58 months. Median progression-free survival (25 vs.
19 months; p = 0.08), progression-free survival 2 (56 vs. 49 months; p = 0.9) and overall survival
(73 months vs. NR; p = 0.08) were not significantly different between the two arms. Toxicity profiles
of lenalidomide-prednisone and lenalidomide were similar, with the exception of neutropenia that
was higher in the lenalidomide arm (grade â„ 3: 9% vs. 19%, p < 0.001), without an increase in the rate
of infections. Overall survival (median NR vs. 49 months, p < 0.001), progression-free survival from
relapse (median 35 vs. 24 months, p = 0.004) and overall survival from relapse (median not reached
vs. 41 months, p = 0.002) were significantly longer in patients continuing maintenance for â„2 years.
We showed that the addition of prednisone at 25 or 50 mg every other day (eod) to lenalidomide
maintenance did not induce any significant advantage
Randomized phase III study (ADMYRE) of plitidepsin in combination with dexamethasone vs. dexamethasone alone in patients with relapsed/refractory multiple myeloma
The randomized phase III ADMYRE trial evaluated plitidepsin plus dexamethasone (DXM) versus DXM alone in patients with
relapsed/refractory multiple myeloma after at least three but not more than six prior regimens, including at least bortezomib and
lenalidomide or thalidomide. Patients were randomly assigned (2:1) to receive plitidepsin 5 mg/m2 on D1 and D15 plus DXM
40 mg on D1, D8, D15, and D22 (arm A, n = 171) or DXM 40 mg on D1, D8, D15, and D22 (arm B, n = 84) q4wk. The primary
endpoint was progression-free survival (PFS). Median PFS without disease progression (PD) confirmation (IRC assessment) was
2.6 months (arm A) and 1.7 months (arm B) (HR = 0.650; p = 0.0054). Median PFS with PD confirmation (investigatorâs
assessment) was 3.8 months (arm A) and 1.9 months (arm B) (HR = 0.611; p = 0.0040). Median overall survival (OS,
intention-to-treat analysis) was 11.6 months (arm A) and 8.9 months (arm B) (HR = 0.797; p = 0.1261). OS improvement
favoring arm A was found when discounting a crossover effect (37 patients crossed over from arm B to arm A) (two-stage
method; HR = 0.622; p = 0.0015). The most common grade 3/4 treatment-related adverse events (% of patients arm A/arm B)
were fatigue (10.8%/1.2%), myalgia (5.4%/0%), and nausea (3.6%/1.2%), being usually transient and reversible. The safety
profile does not overlap with the toxicity observed with other agents used in multiple myeloma. In conclusion, efficacy data, the
reassuring safety profile, and the novel mechanism of action of plitidepsin suggest that this combination can be an alternative
option in patients with relapsed/refractory multiple myeloma after at least three prior therapy lines
Prevention and management of adverse events of novel agents in multiple myeloma: A consensus of the European Myeloma Network
During the last few years, several new drugs have been introduced for treatment of patients with multiple myeloma, which have significantly improved the treatment outcome. All of these novel substances differ at least in part in their mode of action from similar drugs of the same drug class, or are representatives of new drug classes, and as such present with very specific side effect profiles. In this review, we summarize these adverse events, provide information on their prevention, and give practical guidance for monitoring of patients and for management of adverse events
Real-world outcomes and factors impacting treatment choice in relapsed and/or refractory multiple myeloma (RRMM): a comparison of VRd, KRd, and IRd
Lack of head-to-head trials highlights a need for comparative real-world evidence of proteasome
inhibitors plus Rd.
Methods: In this retrospective, US population-representative EHR study of RRMM patients initiating IRd,
KRd, or VRd in line of therapy (LOT) â„2 between 1/2014 and 9/30/2018, 664 patients were treated in
LOT â„2 with: IRd, n = 168; KRd, n = 208; VRd, n = 357. Median age was 71/65/71 years; 67%/70%/75%
had a frailtymodified score of intermediate/frail; 20%/28%/13% had high cytogenetic risk in I-/K-/V-Rd
groups. Risk of PI-triplet discontinuation was lower for I- vs. K-Rd (HR: 0.71) and I- vs. V-Rd (HR: 0.85);
unadjusted, median TTNTs (months): 12.7/8.6/14.2 (LOT â„2) and 16.8/9.5/14.6 (LOT 2â3) (I-/K-/V-Rd).
Adjusted TTNT was comparable between I-/K-/V-Rd in LOT â„2 with a TTNT benefit among intermediate/
frail patients for I- (HR: 0.70; P=0.04) and V- (HR: 0.73; P<0.05) vs. K-Rd. I/K/V-Rd triplets were comparable
in TTNT overall, but IRd and VRd were associated with longer TTNT in intermediate/frail patients than
KRd. The results suggest a trial-efficacy/real-world-effectiveness gap, especially for KRd, underlining the
limited generalizability of trial results where >50% of patients are excluded. Individualized treatment
based on patient characteristics, such as frailty status, is especially pertinent in an elderly RRMM
population