Mantle cell lymphoma (MCL) is a non-Hodgkin lymphoma that is incurable with standard chemotherapy. There is no consensus on the best initial therapy, especially for elderly patients, who are not candidates for aggressive treatment approaches. Current National Comprehensive Cancer Network (NCCN) treatment guidelines include rituximab (R) plus cladribine for the initial treatment of MCL. However, few data are available to substantiate this recommendation. Therefore, to further define the role of R-cladribine for the initial treatment of MCL, we performed a retrospective chart review of 31 patients with MCL (median age, 67) treated with R-cladribine. The majority of responding patients also received R maintenance. The overall response rate was 87%, with 61% of patients achieving a complete remission (CR/CRu). The estimated median follow-up was 32.5 months, median PFS was 37.5 months, and median OS was 85.2 months. One of 19 (5.3%) subjects in CR/CRu relapsed (median follow-up of 23 months). CR/CRu was associated with improved survival (p < 0.0001), while a high mantle cell international prognostic index (MIPI) was associated with worse survival (p = 0.05). There was one toxic death (neutropenic pseudomonal sepsis) related to treatment. R-cladribine is an effective therapy for previously untreated MCL, and these results validate the use of R-cladribine for the initial treatment of MCL.
4910 Background: Mantle cell lymphoma (MCL) is a B-cell non-Hodgkin lymphoma that is incurable with standard chemotherapy and remains a therapeutic challenge. Despite improved outcomes in MCL there is no consensus on the best initial treatment. Options vary from aggressive treatment strategies that incorporate multi-agent induction chemotherapy and consolidative transplant to less intensive treatment strategies that utilize alkylators, purine nucleoside analogues, and the monoclonal antibody rituximab. Although, higher response rates have been seen with aggressive approaches, their impact on overall survival is not yet fully appreciated and many patients are not candidates for such approaches. Thus, finding less intensive induction regimens is imperative. The combination of rituximab plus cladribine has shown activity across a number of B-cell malignancies and the NCCN treatment guidelines currently include this regimen for the initial treatment of MCL; noting that there are few data available to substantiate this recommendation. The largest prospective experience (n=29) with R-cladribine for the initial treatment of MCL comes from the North Central Cancer Group. They reported an overall response rate (ORR) of 66% with a 52% complete remission (CR) rate and a 2 year progression free survival (PFS) of 43%. Given its therapeutic potential and increasing popularity, more data are needed to verify the benefits of the R-cladribine regimen. Therefore, to explore the role of R-cladribine in the treatment of newly diagnosed MCL, we performed a retrospective chart review of patients with newly diagnosed MCL treated with R-cladribine. Methods: We reviewed the charts of 31 patients with newly diagnosed MCL initially seen at two university hospitals and at an associated VA that were treated with R-cladribine. One patient had been previously treated with 2 cycles of R-CHOP;, all other patients were untreated. All patients had measurable disease and follow up imaging (CT and/or PET/CT scans) before and at the completion of therapy. Post treatment bone marrow biopsies were not available for all patients. Chemotherapy included: cladribine 5mg/m2 given over two hours on days 1–5; and rituximab given on days 1, 8, 15, and 22 with the first cycle and then on day 1 with subsequent cycles. Each cycle was 28 days for up to a total of 6 cycles. Patients with an initial response received maintenance rituximab. Results: The median age of our cohort was 67 years (48-86) with 42% of patients ≥ 65 years. All patients had advanced stage disease (stage ≥ 3) and the majority of patients had poor risk disease. For example, 20/31 (65%) of patients had high FLIPI (≥ 3) and11/31 (37%) had high MIPI (≥ 6). Of the 24 patients in whom beta2-microglobulin was available, 11 (46%) had levels ≥ 3.5 mg/L. The overall response rate (ORR) was 87% with 19/31(61%) of patients achieving a complete remission (CR/CRu). At a median follow up of 21.5 months (2-85 months) the 2 year PFS rate is 65% and the OS rate is 74%. For those subjects achieving a CR/CRu with a median follow up of 23 months, 1/19 (5.3%) has relapsed. No significant trends were seen regarding response rate and pre-treatment disease defining parameters including Ki67, beta2-microglobulin, FLIPI, or MIPI. However, CR was associated with improved survival (p = <.0001) while high MIPI was associated with worse survival (p=0.0317). There was one toxic death (neutropenic sepsis) related to treatment. Conclusion: The combination of rituximab plus cladribine appears to be an effective initial therapy in MCL. The higher response rates seen in this series may be the result of patient selection and/or increased rituximab exposure. Rituximab maintenance may also be an important component of ongoing disease control in responding patients. These data support the ongoing evaluation of rituximab plus cladribine in combination with novel agents. Prospective single arm studies incorporating R-cladribine with other novel agents such as vorinostat, bortezomib, or temsirolimus are ongoing. Disclosures: No relevant conflicts of interest to declare.
Patients with post-allogeneic HSCT disease relapse can be treated with salvage chemotherapy but are also candidates for immune suppression withdrawal and/or donor lymphocyte infusion (DLI). A total of 237 adult patients experienced relapse of disease post-allogeneic transplant at our institution between 1995 and 2010. A retrospective institutional analysis was performed on the 52 patients who received DLI in that timeframe. The DLI product infusion doses ranged from 0.07 to 4.0 x 10 8 CD3+ cells. CML patients had the most favorable DLI response rates with 78% (n 5 7) in remission at 3 years. Patients with relapsed AML/ MDS and lymphoid malignancies fared worse with 36% and 21% OS at 3 years respectively. OS was superior in patients in CR prior to DLI (45%) compared to those with active disease (5%) and for patients under the age of 50 (32% vs 21%). Three year OS was observed of 5% for patients who relapsed prior to day +100, 29% for relapse between day +100 and 1 year, and 59% for relapse after 1 year. Patients who developed GvHD prior to relapse had a 3 year OS of 35% vs 9% in patients without GvHD. Patients with post-DLI GvHD had a 39% OS vs 11% for patients without GvHD after DLI. No difference in post-DLI survival was noted with regards to pre-transplant disease status, cell dose or transplant conditioning. CML patients respond well to DLI however in the TKI era, transplants for these patients are reserved for patients with TKI-resistant disease. In other patients, immune suppression withdrawal and DLI have limited efficacy for those who do not achieve CR post-relapse or who relapse within 3 months of transplant. These patients are in need of alternative treatment strategies.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.