Enduring Responses after 1-Year, Fixed-Duration Cevostamab Therapy in Patients with Relapsed/Refractory Multiple Myeloma: Early Experience from a Phase I Study
Bibliographic record
Abstract
Background: Relapsed/refractory multiple myeloma (RRMM) remains an incurable disease, with most treatment regimens continued until disease progression (PD). New treatments that are efficacious when given for a fixed duration and offer the potential for an extended treatment-free period may also decrease cumulative toxicities and reduce the burden of treatment on both patients and healthcare systems. Cevostamab is an FcRH5xCD3 T-cell engaging bispecific monoclonal antibody that facilitates T-cell directed killing of myeloma cells and has demonstrated clinically meaningful activity and a favorable toxicity profile when given Q3W for up to 17 cycles (approximately 1 year) in an ongoing Phase I trial (GO39775; NCT03275103) in patients with heavily pre-treated RRMM (Trudel et al. ASH 2021). Here, we report early duration of response data for patients in GO39775 who completed 17 cycles of cevostamab and stopped treatment. Methods: All patients were aged ≥18 years and had RRMM for which no established therapy was available, appropriate, or tolerable, and an ECOG performance status of 0-1. Cevostamab was administered by intravenous infusion in 21-day cycles with step-up dosing in Cycle (C) 1 for cytokine release syndrome mitigation. Treatment was continued for 17 cycles (approximately 1 year) unless PD or unacceptable toxicity occurred. Patients who achieved a partial response (PR) or better by C17 and maintained a response through C17 were included in the analysis. Results: At data cut-off (March 8, 2022), a total of 16 patients (median age: 66.5 years; range: 45-80) completed C17 of cevostamab treatment and were eligible for analysis. Patients had received a median of 6 prior lines of therapy (range: 2-11), with 12 patients having received ≥5 prior therapies. Thirteen patients were triple-class refractory and 11 were penta-refractory. Fifteen patients were refractory to their last prior therapy. Five patients had received prior anti-B-cell maturation antigen (BCMA) targeted therapies, 4 of whom were refractory to anti-BCMA treatment. Patients received cevostamab target doses ranging from 40-160mg and received a median of 17 cycles of treatment (range: 16-17). Among the 16 patients analyzed, the best overall response (BOR) achieved was: stringent complete response (sCR) in 7 patients, CR in 3 patients, very good partial response (VGPR) in 5 patients, and PR in 1 patient. At data cut-off, 13 of the 16 patients remained in remission, with 8 patients (BOR: 5 sCR, 1 CR, 2 VGPR) maintaining a response ≥6 months after completion of therapy and 3 patients (BOR: 2 sCR, 1 CR) maintaining a response ≥12 months after completion of therapy. Eight patients had <6 months of follow-up. None of the patients (0/10) who completed C17 and attained a sCR or CR had relapsed. Only 3 of the 16 patients (BOR: 2 VGPR, 1 PR) had PD after the completion of C17 of cevostamab. Time to progression following completion of therapy for the 2 patients who achieved a VGPR was 7.8 months and 12.9 months. For the patient who achieved a PR, time to progression was 1.3 months. Due to its mechanism of action, treatment with cevostamab may be associated with an increased risk of infection. Infections occurred in 2 patients after the completion of C17 of cevostamab therapy. Pneumonia was reported in both patients, with onset after the last dose of 1.3 months and 3.8 months. Both events resolved and both patients have remained on study. Conclusions: Early data from this Phase I study suggest that patients can maintain durable responses (≥6 months) after completion of 17 cycles of cevostamab treatment, highlighting the potential for an extended treatment-free period following fixed-duration therapy. Further data are needed to confirm the duration of response and associated correlates following completion of treatment. Additional data on responding patients with premature discontinuation of treatment (i.e. prior to completion of C17) and patients retreated with cevostamab will be presented.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.004 | 0.002 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".