Delayed Efficacy After Treatment With Lenalidomide or Thalidomide in Patients With Mucosa-Associated Lymphoid Tissue Lymphoma

Abstract

Background. The immunomodulatory drugs (IMiDs) thalidomide and lenalidomide have both been tested for treatment of mucosa‐associated lymphoid tissue (MALT) lymphoma, with lenalidomide, in particular, showing promising activity. However, long‐term results are missing. Because of the late‐onset remissions registered in individual patients, we have systemically analyzed the patients treated with IMiDs at our institution for long‐term results. Methods. Within the present retrospective analysis, we identified 25 patients who had been treated with lenalidomide (n = 18) or thalidomide (n = 7) and were available for long‐term assessments of outcome. All patients were followed up according to a standardized follow‐up protocol. Results. Of the 25 patients, 7 (28%) experienced delayed‐onset responses without further treatment (thalidomide, n = 2; lenalidomide, n = 5). In 4 patients (16%), the initial outcome switched to a better result (partial remission [PR] to complete remission [CR], n = 1; stable disease [SD] to PR, n = 1; SD to CR, n = 1; and PD to CR, n = 1) after a median time of 19.5 months (range, 10.9–32.0). Furthermore, 2 patients showed ongoing shrinkage of the target lesion for 47.4+ and 43.5+ months, respectively, and 1 patient had durable disease stabilization for 16.2+ months. The median time to the best response for all responding patients (13 of 25; 53%) was 7.3 months (interquartile range [IQR], 5.6–22.5). After a median follow‐up of 46 months (IQR, 32.0–58.5), 23 of 25 patients (92%) were alive. Conclusion. Our findings suggest that late‐onset remissions might be a common phenomenon in the use of IMiDs for the treatment of MALT lymphoma. Thus, sufficient follow‐up time after treatment before the initiation of further therapy appears crucial to assess the full effect of therapy and avoid unnecessary overtreatment. Implications for Practice: The immunomodulatory drugs (IMiDs) thalidomide and lenalidomide have been tested for the treatment of mucosa‐associated lymphoid tissue (MALT) lymphoma, with lenalidomide showing promising activity. However, long‐term results are missing. The present findings suggest that late‐onset remissions and delayed responses could be a common phenomenon with IMiD use for MALT lymphoma. Using a standardized restaging protocol to ensure concise follow‐up data, these findings suggest it is of major importance to ensure a sufficient follow‐up time after treatment with these compounds and before initiation of further treatment lines, because nearly one third of treated patients showed further improvement during prolonged follow‐up.

A phase 2 study of rituximab plus lenalidomide for mucosa-associated lymphoid tissue lymphoma

“…[12][13][14][15] In addition, late remissions appear to be a common phenomenon in patients treated with immunomodulatory drugs for MALT lymphoma and long-term effects of R-LEN might still be underestimated in the current analysis. 16 In conclusion, the data generated in the AGMT MALT-2 trial suggest R-LEN to be feasible, safe, and active for treating patients with MALT lymphoma irrespective of primary localization and pretreatment.…”

The spectrum of MALT lymphoma at different sites: biological and therapeutic relevance

“…125 The significant hematological and infectious toxicity observed with the latter regimen, both during and after therapy, was deemed too high in this patient population. 125 As shown in Table 4, [126][127][128][129][130][131][132][133][134][135][136][137][138][139][140][141][142][143][144] new targeted agents have been poorly studied in MALT lymphomas: only 3 studies 127,129,133 were restricted to this entity and included .10 patients.…”

Prolonged follow‐up on lenalidomide‐based treatment for mucosa‐associated lymphoid tissue lymphoma (MALT lymphoma)—Real‐world data from the Medical University of Vienna

“…Importantly, a total of four patients showed delayed responses including three patients initially rated as PR converting to a CR at 12 to 32 months, highlighting the potential of late remissions following immunomodulatory treatment in such an indolent disease, a phenomenon that has been reported not only for LEN but also thalidomide in MALT lymphoma patients before. 33 In terms of long-term outcome, at a median follow-up time of 68 months, 54% of patients are free of progression, and the estimated PFS was 72 months in our study. Interestingly, our data suggest a statistically superior PFS for patients achieving a response to LEN-based therapy over patients with SD only (P = .01), and in addition PFS following CR was also longer over PR (P = .05).…”