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Observational study shows good clinical activity for lenalidomide in R/R MCL patients after ibrutinib therapy failure – MCL-004

Nov 10, 2017

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The MCL-004 observational study results were published in the Journal of Hematology & Oncology on 2nd November 2017 by Michael Wang, Department of Lymphoma/Myeloma, University of Texas MD Anderson Cancer Center, Houston, TX and colleagues.

The multicentre (US, Germany, Italy, UK) study evaluated the use of lenalidomide in patients with mantle cell lymphoma (MCL) who relapsed or progressed after failed or intolerable treatment with ibrutinib. The primary endpoint was investigator-assessed overall response rate (ORR), secondary endpoint was duration of response (DOR) and safety was also assessed.            

Study Highlights

  • 58 patients were enrolled in the study (median age = 71 years)
    • Patients received lenalidomide as either monotherapy (n = 13), with rituximab (n = 11) or with another treatment (n = 34)

Key Findings

  • Patients received a median of 2 cycles of lenalidomide treatment (range 0–11)
    • 10–25 mg/day on days 1–21 of a 28-day cycle
  • 17 patients responded: complete response (CR) = 8, partial response (PR) = 9
  • ORR = 29% (n = 17) (95% CI, 18–43%)
    • A subgroup analysis between ibrutinib refractory vs relapsed/progressed patients had similar ORR = 32% vs 30%
  • Median DOR for responders = 20 weeks (95% CI, 2.9–not reached)


  • 83% of patients (n = 48) had one or more treatment-emergent adverse events (TEAEs) during treatment
  • The most frequent serious TEAEs were febrile neutropenia (7%, n = 4), hypotension (7%), deep vein thrombosis (DVT) (5%, n = 3), pneumonia (5%)
  • Most common all-grade TEAEs were fatigue, cough, dizziness, dyspnea, nausea, peripheral edema, anemia, rash, thrombocytopenia, and neutropenia
  • A total of 28 patients (48%) died: this was due to either malignant disease (n = 20), end-stage renal disease (n = 1), AEs (n = 2) or unknown cause of death (n = 5)

Professor Simon Rule, from the Department of Haematology at Plymouth University, UK, who was involved in the MCL-004 study, was interviewed by the Lymphoma Hub at the American Society of Hematology (ASH) 2016 annual meeting. He said that about 30% of patients responded, some with a complete response and commented, “lenalidomide is a very active drug in mantle cell lymphoma, though it tends to be less active in the more proliferative patients”. He added, “in the next couple of years what we do with ibrutinib-failing patients is going to become a very important question.”

The authors of the MCL-004 study concluded that lenalidomide showed clinically significant activity in MCL patients who were relapsed/progressed and intolerant of or failed previous ibrutinib therapy. They added that because the patients had a high number of previous therapy regimens they were considered high-risk and this could have produced more negative results. No new safety signals emerged from this study.


BACKGROUND: The observational MCL-004 study evaluated outcomes in patients with relapsed/refractory mantle cell lymphoma who received lenalidomide-based therapy after ibrutinib failure or intolerance. METHODS: The primary endpoint was investigator-assessed overall response rate based on the 2007 International Working Group criteria. RESULTS: Of 58 enrolled patients (median age, 71 years; range, 50-89), 13 received lenalidomide monotherapy, 11 lenalidomide plus rituximab, and 34 lenalidomide plus other treatment. Most patients (88%) had received ≥ 3 prior therapies (median 4; range, 1-13). Median time from last dose of ibrutinib to the start of lenalidomide was 1.3 weeks (range, 0.1-21.7); 45% of patients had partial responses or better to prior ibrutinib. Primary reasons for ibrutinib discontinuation were lack of efficacy (88%) and ibrutinib toxicity (9%). After a median of two cycles (range, 0-11) of lenalidomide-based treatment, 17 patients responded (8 complete responses, 9 partial responses), for a 29% overall response rate (95% confidence interval, 18-43%) and a median duration of response of 20 weeks (95% confidence interval, 2.9 to not available). Overall response rate to lenalidomide-based therapy was similar for patients with relapsed/progressive disease after previous response to ibrutinib (i.e., ≥PR) versus ibrutinib-refractory (i.e., ≤SD) patients (30 versus 32%, respectively). The most common all-grade treatment-emergent adverse events after lenalidomide-containing therapy (n = 58) were fatigue (38%) and cough, dizziness, dyspnea, nausea, and peripheral edema (19% each). At data cutoff, 28 patients have died, primarily due to mantle cell lymphoma. CONCLUSION: Lenalidomide-based treatment showed clinical activity, with no unexpected toxicities, in patients with relapsed/refractory mantle cell lymphoma who previously failed ibrutinib therapy.

  1. Wang M. et al. Observational study of lenalidomide in patients with mantle cell lymphoma who relapsed/progressed after or were refractory/intolerant to ibrutinib (MCL-004). Journal of Hematology Oncology. 2017 Nov 2;10(1):171. DOI: 10.1186/s13045-017-0537-5.

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