Maintenance rituximab after autologous stem cell transplantation in patients with mantle cell lymphoma

Graf, Solomon A.; Stevenson, Philip A.; Holmberg, Leona; Till, Brian G.; Press, Oliver W.; Chauncey, Thomas R.; Smith, Stephen D.; Philip, Mary; Orozco, Johnnie J.; Shustov, Andrei R.; Green, D. J.; Libby, Edward N.; Bensinger, William I.; Pagel, John M.; Maloney, David G.; Zhou, Yi; Cassaday, Ryan D.; Gopal, Ajay K.

doi:10.1093/annonc/mdv364

Cited by 35 publications

(19 citation statements)

References 23 publications

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“…In fact, patients who received maintenance rituximab had a 75% risk reduction in progression and 83% in death. Two other retrospective studies have also reported a benefit of rituximab maintenance in PFS and potentially OS when given post-ASCT (17, 18); nevertheless, our study has the largest number of patients. The only prospective randomized trial of post-ASCT maintenance rituximab is the phase 3 LyMa study, and the results were recently presented in ASH 2016.…”

Section: Discussionmentioning

confidence: 78%

Long-Term Results of High-Dose Therapy and Autologous Stem Cell Transplantation for Mantle Cell Lymphoma: Effectiveness of Maintenance Rituximab

Mei

Cao

Chen

et al. 2017

Biology of Blood and Marrow Transplantation

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High-dose therapy followed by autologous stem cell transplantation (ASCT) can improve outcomes for mantle cell lymphoma (MCL) but is associated with a high incidence of relapse. A retrospective study of 191 MCL patients who underwent ASCT at City of Hope was performed to examine prognostic factors for outcomes following ASCT. For all patients, the 5-year overall survival (OS) was 71% (confidence interval [CI]: 63% – 77%) and progression-free survival (PFS) was 53% (CI: 45% – 60%). The 5-year cumulative incidence of relapse was 41% (CI: 34% – 48%) with a continuous pattern of relapse events occurring at a median of 2.1 years (range: 0.2 – 13.4) after ASCT. In multivariate analysis, post-transplant maintenance rituximab was the factor most significantly associated with both OS (relative risk [RR] 0.17, CI: 0.07 – 0.38) and PFS (RR 0.25, CI: 0.14 – 0.44). For the subset of patients who had positron emission tomography (PET) data available and were in a PET-negative first complete remission (CR1) at ASCT (n = 105), Maintenance rituximab was significantly associated with superior OS (RR 0.17, CI: 0.05 – 0.59) and PFS (RR 0.20, CI: 0.09 – 0.43). These results support a benefit with maintenance rituximab for all MCL patients treated with ASCT.

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Section: Discussionmentioning

confidence: 78%

Long-Term Results of High-Dose Therapy and Autologous Stem Cell Transplantation for Mantle Cell Lymphoma: Effectiveness of Maintenance Rituximab

Mei

Cao

Chen

et al. 2017

Biology of Blood and Marrow Transplantation

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“…On multivariate analysis, MR therapy was associated with improved PFS (hazard ratio (HR) = 0.23; 95% confidence interval (CI) = 0.06-0.80), although no OS benefit was noted (HR = 0.61, 95% CI = 0.14-2.65). 31 Graf et al 32 similarly examined a cohort of patients which underwent ASCT followed by MR or observation. Although various rituximab administration schedules were evaluated, on multivariate analysis MR was associated with improved PFS (HR = 0.44; 95% CI = 0.24-0.80) along with OS (HR = 0.46; 95% CI = 0.23-0.93).…”

Section: Mantle Cell Lymphomamentioning

confidence: 99%

“…Although various rituximab administration schedules were evaluated, on multivariate analysis MR was associated with improved PFS (HR = 0.44; 95% CI = 0.24-0.80) along with OS (HR = 0.46; 95% CI = 0.23-0.93). 32 Recently, prospective studies have further investigated the role of maintenance therapy post ASCT in MCL. In the LYMA study, patients who achieved a PR or CR to high-dose chemotherapy followed by ASCT were randomized to either observation or MR (375 mg/m 2 every 2 months for 3 years).…”

Section: Mantle Cell Lymphomamentioning

confidence: 99%

“…A PFS benefit for MR has been reproducible through these various studies, though no firm conclusions can be drawn regarding an OS advantage. [31][32][33] Given the aggressive and incurable nature of MCL, it is important that practitioners weigh the risks and benefits of post-ASCT MR therapy. One must consider the toxicities associated with these maintenance regimens, along with the increased cost and other logistical concerns.…”

Section: Mantle Cell Lymphomamentioning

confidence: 99%

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Post-autologous transplant maintenance therapies in lymphoma: current state and future directions

Riedell

Bishop

2017

Bone Marrow Transplant

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Disease relapse following high-dose chemotherapy and autologous stem cell transplant (ASCT) remains the principal cause of mortality in patients with relapsed or refractory lymphomas. In an effort to prevent post-ASCT relapse, a number of studies have evaluated the role of maintenance therapy with varying success. In diffuse large B-cell lymphoma, studies evaluating maintenance rituximab (MR) following ASCT failed to demonstrate improved outcomes. In follicular lymphoma, MR was associated with an improvement in PFS; however, no overall survival (OS) benefit was noted. Emerging data evaluating MR in mantle cell lymphoma (MCL) have demonstrated improvements in PFS, although a consistent improvement in OS has yet to be demonstrated. Given the aggressive and incurable nature of MCL, it is prudent for practitioners to weigh the risks and benefits of MR in the post-ASCT setting. Similarly, post-ASCT maintenance therapy with brentuximab vedotin in Hodgkin lymphoma, has led to improved PFS and may be considered in those with a high risk of relapse. Ongoing clinical studies evaluating a multitude of novel maintenance therapies are crucial to the efforts of further defining and optimizing the role of post-transplant maintenance therapy in lymphoma.

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“…Several retrospective and a few prospective studies have evaluated maintenance rituximab in MCL (Table 2). [84][85][86][87] Dietrich et al…”

Section: Mantle Cell Lymphoma (Mcl)mentioning

confidence: 99%

Post-autologous transplant maintenance therapies in lymphoid malignancies: are we there yet?

Epperla

Fenske

Lazarus

et al. 2015

Bone Marrow Transplant

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Disease relapse after autologous hematopoietic transplant (auto-HCT) remains the number one cause of post-transplant therapy failure and mortality. The last decade has seen a proliferation of clinical studies looking at the prevention of post-auto-HCT therapy failure with various maintenance strategies. The benefit of such therapies is in turn dependent on disease histology and timing of transplantation. Although high dose therapy (HDT) provides durable responses in chemosensitive relapsed diffuse large B-cell lymphoma (DLBCL), a sizable subset experiences disease relapse. Unfortunately, the addition of rituximab as a post-auto-HCT maintenance strategy did not improve survival outcomes. The preliminary results with programmed death -1 (PD-1) Ab as post-auto maintenance in DLBCL is promising but requires randomized validation. In follicular lymphoma, the 5-and 10-year PFS rates are~60% and 31%, respectively. Although the addition of rituximab improved PFS, there is no survival benefit, to date. Disease relapse after auto-HCT in mantle cell lymphoma (MCL) is not uncommon. Rituximab maintenance in this setting provides a PFS benefit. Given the poor prognosis of post-auto-HCT failures in MCL, maintenance can be considered on a case-by-case basis. In chemosensitive relapsed Hodgkin lymphoma, addition of brentuximab vedotin after auto-HCT improved 2-year PFS (65 vs 45%) and can be considered as an option for maintenance therapy post auto-HCT, in select higher risk patients. Ongoing trials evaluating the efficacy of post-auto-HCT maintenance with novel agents (for example, immunomodulators, proteasome inhibitors, PD-1 inhibitors, Bruton's tyrosine kinase inhibitors and so on) will likely change the practice landscape for lymphoma patients following HDT and auto-HCT.

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Maintenance rituximab after autologous stem cell transplantation in patients with mantle cell lymphoma

Abstract: These data support that MR after ASCT for MCL confers a benefit in PFS and additionally suggest it may improve OS. General application of this strategy will require confirmation of benefit in prospective randomized trials.

Cited by 35 publications

References 23 publications

Long-Term Results of High-Dose Therapy and Autologous Stem Cell Transplantation for Mantle Cell Lymphoma: Effectiveness of Maintenance Rituximab

Long-Term Results of High-Dose Therapy and Autologous Stem Cell Transplantation for Mantle Cell Lymphoma: Effectiveness of Maintenance Rituximab

Post-autologous transplant maintenance therapies in lymphoma: current state and future directions

Post-autologous transplant maintenance therapies in lymphoid malignancies: are we there yet?

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