Drug class refractoriness, not number of prior lines of therapy, properly classify patients with relapsed and refractory multiple myeloma

Subsequent therapy and outcomes in patients with newly diagnosed multiple myeloma experiencing disease progression after quadruplet combinations

“…For instance, in the MAMMOTH study, median PFS and OS were 3.4 and 9.3 months, 18 respectively, while in the prospective LOCOMMOTION study, 20 median PFS and OS were 4.6 and 12.4 months. The outcomes here described confirm our prior observation than exposure and refractoriness shape the likelihood of response and overall prognosis in RRMM and entirely displace the number of prior lines of therapy 26,27 . This is particularly concerning given that approval of new therapies in myeloma follows a paradigm of a number of prior lines of therapies, leaving these patients with no reasonable therapeutic option outside clinical trials.…”

“…The outcomes here described confirm our prior observation than exposure and refractoriness shape the likelihood of response and overall prognosis in RRMM and entirely displace the number of prior lines of therapy. 26,27 This is particularly concerning given that approval of new therapies in myeloma follows a paradigm of a number of prior lines of therapies, leaving these patients with no reasonable therapeutic option outside clinical trials. Another sobering observation is that despite half the patients with progression <18 months in our cohort eventually receiving a T-cell redirecting therapy, mostly through clinical trial participation, the outcomes were still unsatisfactory.…”

“…Moreover, the results highlight the limitations of clinical trial enrolment and the regulatory approval process based on the number of prior lines of therapy, a process that indirectly penalizes the early combined use of more active agents with higher efficacy. 26,27 QUAD/ASCT-treated patients experiencing progression <18 months characterize an unmet medical need population in urgent need for innovation.…”

Outcomes of patients with primary refractory multiple myeloma in the era of triplet and quadruplet induction therapy

“…Although the second PFS (5.4 months vs 12.1 months, respectively) and second OS (21.7 vs 48.3 months, respectively) of clinical PD were numerically shorter, they did not reach our statistical significance threshold, probably because of the small number of patients ( supplemental Figures 2 and 3 ). Of the patients with known subsequent treatment, 33 (49.3%) received salvage chemotherapy and ASCT as the second-line therapy, whereas 23 (34.2%) 18 received daratumumab as part of their second-line therapy. For patients who underwent salvage ASCT, no statistically significant differences were observed in the baseline and clinical characteristics compared with those who did not, although the median age was 60.9 vs 67.2 years, respectively ( P = .51; Table 2 ).…”

Inclusion criteria of currently enrolling T‐cell engaging trials in multiple myeloma: Should we be focusing on lines of prior therapy?

“…European regulatory approval and reimbursement also strictly follow these labels, and inclusion of a minimum number of line of therapies in the approval label may prevent access for some patients. Given that class refractoriness has been shown to be a much more important determinant of prognosis than lines of therapy in recent studies, [6][7][8] we urge these currently enrolling clinical trials to amend their protocols and allow for broader enrollment of patients that may benefit most from these treatments. As these inclusion criteria requirements may be due to regulations by the FDA and European authorities, greater regulatory flexibility in these inclusion criteria may allow for more patients to receive these treatments in the future.…”