Transplant for Mantle-Cell Lymphoma: Is it the Right Thing to Do?

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During the 2013 Annual Meeting of the American Society of Hematology, Michael E Williams, MD, chaired an educational session titled, “Transplant for Mantle-Cell Lymphoma: Is it the Right Thing to Do?”, in which he presented clinical progress and current challenges in the treatment of patients with mantle-cell lymphoma (MCL).1 Dr Williams is Byrd S Leavell Professor of Medicine and Chief of the Hematologic Malignancies Section at the Hematology/Oncology Division and Cancer Center at the University of Virginia School of Medicine.

In his opening, Dr Williams highlighted the following areas of advancement in MCL related to diagnosis, treatment, and clinical outcomes:

  • MCL diagnosis is now straightforward because of the identification of unique cytogenetic markers of MCL, specifically the chromosomal translocation that dysregulates cyclin D1 expression.1
  • Calculation of the MIPI (MCL International Prognostic Index) score helps clinicians determine the overall survival prognosis for newly diagnosed patients.1
  • Availability of novel agents targeting various aspects of cell signaling, cell division, and apoptosis has significantly improved overall survival outcomes.1

Challenges that remain in the management of MCL relate to disease pathogenesis, optimal selection and sequencing of therapies, and patient participation in clinical trials that evaluate novel treatment strategies. Dr Williams also noted that the optimal time to initiate therapy is unresolved in both younger patients and older patients who have comorbidities, and particularly in those patients with the indolent disease.1

Prior to summarizing results from various phase 3 trials that evaluated cytotoxic combinations and autologous stem-cell transplantation (ASCT), Dr Williams reviewed key clinical goals in the management of patients with newly diagnosed MCL:

  • Obtain a deep and durable remission
  • Maximize time between cytotoxic treatments
  • Do not burn bridges with future treatment options
  • Minimize early and late toxicities

Despite multiple clinical trials exploring the use of cytotoxic and chemoimmunotherapy combinations in newly diagnosed MCL, Dr Williams ended his discussion on first-line MCL therapy by saying, “It is fair to say that the standard of care is not established. It is important to keep in mind that for that subset of indolent patients, it is certainly OK to watch and wait.”1 For younger, fit patients with MCL, Dr Williams recommended high-dose cytarabine-containing regimens plus rituximab, followed by ASCT. He noted that elderly patients with MCL who have comorbidities should receive rituximab plus bendamustine or R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone), followed by rituximab maintenance.1

In the context of relapsed or refractory MCL, Dr Williams highlighted recently published data for ibrutinib and lenalidomide, 2 agents that were FDA approved in 2013 for this patient population.1 He noted that ibrutinib has shown the “highest single-agent responses that we have seen to date in relapsed and refractory MCL”, based on a phase 2 trial in 111 patients with relapsed or refractory MCL.2 This trial documented a 68% overall response rate, median duration of response of 17.5 months, and a median progression-free survival of 13.9 months.2 The most common treatment-related adverse events (AEs) with ibrutinib were mild or moderate diarrhea, fatigue, and nausea.2 Rates of hematologic AEs and discontinuation of treatment due to AEs were low.2

Dr Williams stated that lenalidomide “works in a variety of ways…including immunomodulation and direct antiproliferative effects.”1 The phase 2 study supporting its FDA approval demonstrated that lenalidomide monotherapy is active and safe in patients with MCL who relapsed or progressed after or were refractory to treatment with bortezomib.3 According to independent central review, the overall response rate associated with lenalidomide treatment was 28%, the median duration of response was 16.6 months, and the median progression-free survival was 4.0 months.3 According to Dr Williams, both ibrutinib and lenalidomide are being studied in patients with untreated MCL.1
           
To conclude his presentation, Dr Williams predicted improvements in our understanding of MCL (including molecular and pathogenic insights), movement toward more risk-adapted therapies, novel maintenance and consolidation approaches, and a continued role of ASCT for patients with MCL who are younger and fit.1 He suggested, however, that the role of ASCT may diminish as oncologists’ knowledge of novel therapies evolves, advising the audience to “Stay tuned!”1

References

  1. Williams ME. Transplant for mantle cell lymphoma: is it the right thing to do? Educational program presented at: American Society of Hematology (ASH) Annual Meeting, December 7-10, 2013; New Orleans, LA.
  2. Wang ML, Rule S, Martin P, et al. Targeting BTK with ibrutinib in relapsed or refractory mantle cell lymphoma. N Engl J Med. 2013;369:507-516.
  3. Goy A, Sinha R, Williams ME, et al. Single-Agent Lenalidomide in Patients With Mantle cell Lymphoma Who Relapsed or Progressed After or Were Refractory to Bortezomib: Phase II MCL-001 (EMERGE) Study. J Clin Oncol. 2013;31:3688-3695.
Last modified: March 25, 2014
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