Weekly <i>versus</i> twice weekly bortezomib given in conjunction with rituximab, in patients with recurrent follicular lymphoma, mantle cell lymphoma and Waldenström macroglobulinaemia

Agathocleous, A.; Rohatiner, A. Z. S.; Rule, Simon; Hunter, Hannah; Kerr, Jonathan P.; Neeson, Susan M; Matthews, Janet; Strauss, Sandra J.; Montoto, Silvia; Johnson, Peter; Radford, John; Lister, Andrew

doi:10.1111/j.1365-2141.2010.08340.x

Cited by 65 publications

(41 citation statements)

References 50 publications

(67 reference statements)

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“…Bortezomib may not only be combined with rituximab, 37,39 but also with cytarabine, 40 fludarabine, 41 and even polychemotherapy. 42 Although the actual numbers of MCL patients in trials of such combinations are very small, the combinations do appear to have greater efficacy compared to bortezomib alone.…”

Section: Discussionmentioning

confidence: 99%

“…Neuropathy also developed frequently in a recent trial of bortezomib in MALT lymphoma, in which the dose of bortezomib was 1.5 mg/m 2 administered twice weekly. 38 Besides the early dose modification of bortezomib, alternative doses and schedules of bortezomib should be considered in lymphoma patients, 39 in particular if bortezomib is used after prior administration of neurotoxic agents.…”

Section: Discussionmentioning

confidence: 99%

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Bortezomib combined with rituximab and dexamethasone is an active regimen for patients with relapsed and chemotherapy-refractory mantle cell lymphoma

Lamm¹,

Kaufmann²,

Raderer³

et al. 2011

Haematologica

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BackgroundBortezomib belongs to a new class of anti-cancer agents, the proteasome inhibitors, and has documented activity in multiple myeloma and mantle cell lymphoma. Preclinical studies suggest that bortezomib has synergistic activity with rituximab, which provides a rationale for the exploration of treatment combinations. Design and MethodsThe activity and safety of bortezomib in combination with rituximab and dexamethasone were investigated in patients with relapsed or chemotherapy-refractory mantle cell lymphoma. A treatment cycle consisted of bortezomib (1.3 mg/m 2 on days 1, 4, 8, and 11; six 21-day cycles), rituximab (375 mg/m 2 , day 1) and dexamethasone (40 mg orally, days 1 to 4). Responding patients received four consolidating doses of rituximab. Sixteen patients with progressive mantle cell lymphoma after a median of three prior lines of therapy were enrolled. ResultsThe overall response rate was 81.3% (13 patients), with seven patients achieving a complete response (43.8%). Six of these patients were also negative for disease activity by positron emission tomography scanning. The median progression-free survival and overall survival were 12.1 and 38.6 months, respectively. In patients achieving a complete response, the median progression-free survival and overall survival have not yet been reached. Adverse events (greater than grade II) included thrombocytopenia (37.5%), fatigue (18.8%) and peripheral neuropathy (12.5%). Two patients discontinued bortezomib because of grade III neuropathy. ConclusionsBortezomib combined with rituximab and dexamethasone has promising activity and manageable toxicity in patients with heavily pretreated mantle cell lymphoma. Achievement of complete response emerged as an important factor for sustained disease control. This trial was registered at www.clinicaltrials.gov as #NCT00261612.Key words: bortezomib, rituximab, mantle cell lymphoma, relapse. Haematologica 2011;96(7):1008-1014. doi:10.3324/haematol.2011 Bortezomib combined with rituximab and dexamethasone is an active regimen for patients with relapsed and chemotherapy-refractory mantle cell lymphoma Citation: Lamm W, Kaufmann H, Raderer M, Hoffmann M, Chott A, Zielinski C, and Drach J. Bortezomib combined with rituximab and dexamethasone is an active regimen for patients with relapsed and chemotherapy-refractory mantle cell lymphoma.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Bortezomib combined with rituximab and dexamethasone is an active regimen for patients with relapsed and chemotherapy-refractory mantle cell lymphoma

Lamm¹,

Kaufmann²,

Raderer³

et al. 2011

Haematologica

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“…Randomized comparisons generally reported similar efficacies for the twice-weekly schedule and the once-weekly schedule [100,108,119,121,159,160]. But, as noted above, weekly dosing of bortezomib in combination regimens led to better tolerability than with the twice-weekly dosing schedule in some of those studies [108,121,159,160]. In our practice, we typically administer bortezomib as a single agent, either i.v.…”

Section: Dosingmentioning

confidence: 99%

“…Some studies have suggested that weekly dosing of bortezomib (instead of twice weekly) in combination regimens may improve tolerability [108,121,159,160].…”

Section: Tolerabilitymentioning

confidence: 99%

Proteasome Inhibition and Combination Therapy for Non-Hodgkin's Lymphoma: From Bench to Bedside

2012

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Although patients with B-cell non-Hodgkin's lymphoma (NHL) usually respond to initial conventional chemotherapy, they often relapse and mortality has continued to increase over the last three decades in spite of salvage therapy or high dose therapy and stem cell transplantation. Outcomes vary by subtype, but there continues to be a need for novel options that can help overcome chemotherapy resistance, offer new options as consolidation or maintenance therapy postinduction, and offer potentially less toxic combinations, especially in the elderly population. The bulk of these emerging novel agents for cancer treatment target important biological cellular processes. Bortezomib is the first in the class of proteasome inhibitors (PIs), which target the critical process of intracellular protein degradation or recycling and editing through the proteasome. Bortezomib is approved for the treatment of relapsed or refractory mantle cell lymphoma.The mechanisms of proteasome inhibition are very complex by nature (because they affect many pathways) and not fully understood. However, mechanisms of action shared by bortezomib and investigational PIs such as carfilzomib, marizomib, ONX-0912, and MLN9708 are distinct from those of other NHL treatments, making them attractive options for combination therapy. Preclinical evidence suggests that the PIs have additive and/or synergistic activity with a large number of agents both in vitro and in vivo, from cytotoxics to new biologicals, supporting a growing number of combination studies currently underway in NHL patients, as reviewed in this article. The results of these studies will help our understanding about how to best integrate proteasome inhibition in the management of NHL and continue to improve patient outcomes. The Oncologist 2012; 17:694 -707 OVERVIEWIn the U.S., Ͼ70,000 patients are diagnosed with non-Hodgkin's lymphoma (NHL) annually [1], and one in three patients dies within 5 years of diagnosis [2]. Of note, the incidence of NHL has increased dramatically (Ͼ80% over the last three decades). The broad spectrum of malignancies comprising NHL can be classified according to cell of origin (B, T, or natural killer cell), as well as mature or immature phenotype, as seen in the World Health Organization classification (Table 1) [3,4].The distribution of the different subtypes of NHL varies geographically worldwide.Response rates to conventional chemotherapy are typically Ͼ50%, and many patients achieve a complete response (CR). Even so, most patients eventually relapse [5], and there is no generally accepted therapeutic approach for relapsed or refractory lymphoma the objective response rate (ORR) and CR rate and has been the main improvement in the treatment of B-cell NHL during the last three decades. Though it varies with B-cell NHL subtype, a significant number of patients relapse with no greatly defined standard therapies. For DLBCL, the combination of high-dose chemotherapy and stem cell transplantation is effective for relapsed NHL [7] but is clearly worse in p...

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“…Rituximab, 7 chlorambucil, 8 alkylating agent combinations, 9 R-CHOP (rituximab, CY, doxorubicin (hydroxydaunorubicin), VCR (Oncovin) and prednisone) 10,11 and purine nucleoside analogs 12,13 have all produced high response rates, and many of the responses are durable. Recently, bortezomib 14,15 and bendamustine 16 have both been shown to be highly active in the management of Waldenströ m macroglobulinemia. Investigations into the use of the mTOR inhibitor everolimus 17 have shown it to be useful in heavily pretreated Waldenströ m macroglobulinemia.…”

Section: Why Consider a Transplant In This Disease?mentioning

confidence: 99%

Stem cell transplant for Waldenström macroglobulinemia: an underutilized technique

Gertz

Reeder

Kyle

et al. 2011

Bone Marrow Transplant

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Waldenströ m macroglobulinemia is a highly chemosensitive lymphoplasmacytic lymphoma with response rates of 90% to firstline chemotherapy. The fraction of patients undergoing stem cell transplant for this disorder appears to be lower than that of patients with multiple myeloma. The indolent nature and favorable genetic profile should make Waldenströ m an ideal disorder for autologous stem cell transplant, with high response rates that are durable. We review the literature on autologous and allogeneic transplants for Waldenströ m macroglobulinemia and conclude that autologous transplant is effective and underutilized in the management of this disorder. Allogeneic transplant should be considered investigational and used only in the context of a clinical trial or when other chemotherapeutic options have been exhausted.

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Weekly versus twice weekly bortezomib given in conjunction with rituximab, in patients with recurrent follicular lymphoma, mantle cell lymphoma and Waldenström macroglobulinaemia

Cited by 65 publications

References 50 publications

Bortezomib combined with rituximab and dexamethasone is an active regimen for patients with relapsed and chemotherapy-refractory mantle cell lymphoma

Bortezomib combined with rituximab and dexamethasone is an active regimen for patients with relapsed and chemotherapy-refractory mantle cell lymphoma

Proteasome Inhibition and Combination Therapy for Non-Hodgkin's Lymphoma: From Bench to Bedside

Stem cell transplant for Waldenström macroglobulinemia: an underutilized technique

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