Faculty Opinions recommendation of Phase II study of yttrium-90-ibritumomab tiuxetan in patients with relapsed or refractory mantle cell lymphoma.

PurposeThis phase II trial evaluated the safety and efficacy of yttrium-90 (90Y)–ibritumomab tiuxetan in patients with relapsed or refractory mantle cell lymphoma (MCL).Patients and MethodsPatients with relapsed or refractory MCL were eligible for the study if they had adequate major organ function and performance status. Those with CNS disease, pleural effusion, circulating lymphoma cells ≥ 5,000/μL, or history of stem-cell transplant were ineligible. Patients with a platelet count ≥ 150,000/μL received a dose of 0.4 mCi/kg of90Y–ibritumomab tiuxetan, whereas those with a platelet count less than 150,000/μL received a dose of 0.3 mCi/kg.ResultsThirty-four patients with a median age of 68 years (range, 52 to 79 years) received the therapeutic dose. The patients had received a median of three prior treatment regimens (range, one to six treatment regimens), including those that contained rituximab (n = 32) and bortezomib (n = 7). Of the 32 patients with measurable disease, 10 (31%) achieved complete or partial remission. After a median follow-up of 22 months (range, 2 to 72+ months), an intent-to-treat analysis revealed a median event-free survival (EFS) duration of 6 months and an overall survival duration of 21 months. The median EFS for those who achieved partial or complete remission was 28 months, while it was 3 months for those whose disease did not respond (P < .0001); it was 9 months for patients whose tumor measured less than 5 cm in the largest diameter before treatment and 3 months for those whose tumor measured ≥ 5 cm (P = .015).ConclusionThe single-agent activity of90Y–ibritumomab tiuxetan and its favorable safety profile warrant its further development for the treatment of MCL.

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Phase II Study of Yttrium 90 (90Y) Ibritumomab Tiuxetan (Zevalin®) in Patients with Relapsed and Refractory Mantle Cell Lymphoma (MCL).

Blood ◽

10.1182/blood.v108.11.2714.2714 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2714-2714 ◽

Cited By ~ 7

Author(s):

Michael Wang ◽

Yasuhiro Oki ◽

Barbara Pro ◽

Jorge Enrique Romaguera ◽

Maria Alma Rodriguez ◽

...

Keyword(s):

Mantle Cell Lymphoma ◽

Phase Ii ◽

Cell Lymphoma ◽

Performance Status ◽

Ibritumomab Tiuxetan ◽

Platelet Counts ◽

Mantle Cell ◽

Previously Treated ◽

Grade 3 ◽

Yttrium 90

Abstract Background: Mantle cell lymphoma (MCL) has poor clinical outcome and is a significant therapeutic challenge in patients with relapsed or refractory disease due to its resistance to salvage chemotherapy. Although recent studies have shown the clinical utility of radioimmunotherapy (RIT) in relapsed and transformed indolent B-cell lymphoma, the clinical efficacy of this treatment modality in patients with MCL is not well described. We report the results of a completed phase II clinical trial of yttrium 90 ibritumomab tiuxetan (Zevalin) in patients with relapsed and refractory MCL. Patients and Methods: Patients with relapsed or refractory MCL with measurable disease, age ≥18 years, and performance status <3 were eligible. Patients were required to have adequate function of the bone marrow (ANC ≥1,500/mm3, platelets ≥100,000/mm3), liver, and kidneys. Patients were excluded if they had prior stem cell transplantation, RIT, CNS lymphoma, HIV infection, pleural effusion, HAMA reactivity, or circulating lymphoma cell count ≥5,000/mm3. Patients with pretreatment platelet counts ≥150,000/mm3 received a dose of Zevalin at 0.4 mCi 90Y/kg (maximum dose 32 mCi), whereas those with platelet counts <150,000/mm3 received 0.3 mCi 90Y/kg. Results: Thirty-five patients were enrolled at MDACC. The median age was 68 years (range 52–79), and 27 patients were men. All patients had an ECOG performance status of 0 or 1 and had been previously treated with rituximab with or without other chemotherapy. The median number of prior regimens was 3 (range 1–6). Twelve of the patients did not respond to their last regimen. Twenty-two patients were previously treated with Hyper-CVAD alternating with MTX/Ara-C, and 7 previously received bortezomib. Thirty-one of 35 patients are eligible for evaluation of treatment response and toxicity. There were no grade 3 or 4 non-hematologic toxic events. Grade 1 non-hematologic toxic events included fatigue in 7 and nausea in 3. Grade 2 non-hematologic toxic events included non-neutropenic fever in 1 and melana in 1. Grade 3 or 4 hematologic toxic events included thrombocytopenia in 8, neutropenia in 2 and anemia in 1. Objective responses were observed in 13/31 patients for an overall response rate (ORR) of 42% including 8 CR/CRu’s (26%) and 5 PR’s (16%). Three patients had stable disease. Among the 4 patients who received a Zevalin dose of 0.3 mCi 90Y/kg, 1 achieved a CRu while the 3 others had progressive disease. Eight of the 13 responding patients were previously treated with 3 or more regimens; two patients achieved CR after having received 4 prior lines of therapy. Median progression free survival for the responded patients was 6 months after a median follow up time of 16 months. Conclusion: Zevalin treatment was generally well tolerated; with the most common toxicity being hematological. The observed responses to Zevalin in heavily pretreated patients with MCL are promising and warrant further investigation of its activity after first or second relapse, and in conjunction with front-line therapy.

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Toxicity of fludarabine and cyclophosphamide with or without rituximab as initial therapy for patients with previously untreated mantle cell lymphoma: results of a randomised phase II study

Leukemia & Lymphoma ◽

10.1080/10428190802688509 ◽

2009 ◽

Vol 50 (2) ◽

pp. 211-215 ◽

Cited By ~ 16

Author(s):

Heather E. Eve ◽

David Linch ◽

Wendi Qian ◽

Moira Ross ◽

John F. Seymour ◽

...

Keyword(s):

Mantle Cell Lymphoma ◽

Phase Ii ◽

Phase Ii Study ◽

Cell Lymphoma ◽

Initial Therapy ◽

Mantle Cell

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Durable Responses with Bendamustine Monotherapy In Patients with Relapsed/Refractory Indolent B-Cell Non-Hodgkin Lymphoma (B-NHL) and Mantle-Cell Lymphoma (MCL): Updated Follow-up Data From a Japanese Multicenter Phase II Study

Blood ◽

10.1182/blood.v116.21.4884.4884 ◽

2010 ◽

Vol 116 (21) ◽

pp. 4884-4884 ◽

Cited By ~ 1

Author(s):

Kuniaki Itoh ◽

Kiyoshi Ando ◽

Michinori Ogura ◽

Kenichi Ishizawa ◽

Takashi Watanabe ◽

...

Keyword(s):

B Cell ◽

Mantle Cell Lymphoma ◽

Phase Ii ◽

Group Performance ◽

Phase Ii Study ◽

Cell Lymphoma ◽

Multicenter Phase ◽

Short Period ◽

Mantle Cell

Abstract Abstract 4884 Background: Bendamustine is an alkylating agent with a unique mechanism of action and has demonstrated efficacy as a single agent for the treatment of relapsed or refractory indolent B-NHL or MCL. We conducted a multicenter, phase II study of bendamustine in Japanese patients with indolent B-cell NHL or MCL, reporting an overall response rate of 91% (90% in indolent B-NHL and 100% in MCL) according to International Workshop Response Criteria after a median follow-up of 12.6 months (Ohmachi et al. Cancer Sci 2010 [Epub ahead of print]). Here we report the updated progression-free survival (PFS) data, including median PFS, which had not been reached at the time of previous reports. Patients and Methods: Eligible patients (aged 20–75 years; Eastern Cooperative Oncology Group performance status of 0 or 1) with measurable, pathologically confirmed indolent B-NHL or MCL that failed to respond to, or relapsed after, prior therapy were enrolled. Bendamustine 120 mg/m2 was administered intravenously over 60 minutes on days 1 and 2 every 21 days for up to 6 cycles. PFS was assessed 3 months after completion of the last cycle, and then at 3-month intervals. Results: A total of 69 patients, aged 33–75 years, were enrolled: 58 with indolent B-NHL, mainly follicular lymphoma (n = 52), and 11 with MCL. Patients had primarily stage III or IV disease. The median number of prior regimens was 2 (range, 1–9) for patients with indolent B-NHL and 4 (range, 1–16) for those with MCL. A median of 5 (range, 1–6) bendamustine cycles were administered, with 72% of patients completing 3 or more cycles. The median follow-up time for all patients is 20.6 months (range, 2.5–27.2 months). The median PFS was 21.1 months (95% CI, 15.8-NA; NA = not available due to short period of observation): 20.0 months (95% CI, 12.3-NA) in indolent B-NHL, and 21.7 months (95% CI, 16.5-NA) in MCL. Estimated 2-year PFS rates were 45.2% and 34.1% in indolent B-NHL and MCL, respectively. Conclusions: Bendamustine monotherapy is highly effective in patients with relapsed or refractory indolent B-NHL and MCL. The durable responses observed in this study strongly support the use of bendamustine in these patients and are particularly encouraging in the relapsed or refractory MCL population. Disclosures: Off Label Use: Bendamustine is a novel alkylator that has shown efficacy and safety in patients with indolent lymphomas, and particularly encouraging is the activity in patients with mantle cell lymphoma, which is difficult to treat. Although bendamustine is currently investigational in Japan, approval for relapsed/refractory indolent NHL and mantle cell lymphoma is anticipated in October 2010.

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Combined rituximab, bendamustine, and dexamethasone chemotherapy for relapsed or refractory indolent B-cell non-Hodgkin lymphoma and mantle cell lymphoma: a multicenter phase II study

International Journal of Hematology ◽

10.1007/s12185-019-02650-w ◽

2019 ◽

Vol 110 (1) ◽

pp. 77-85

Author(s):

Yosuke Matsumoto ◽

◽

Tsutomu Kobayashi ◽

Yuji Shimura ◽

Eri Kawata ◽

...

Keyword(s):

B Cell ◽

Mantle Cell Lymphoma ◽

Hodgkin Lymphoma ◽

Phase Ii ◽

Phase Ii Study ◽

Cell Lymphoma ◽

Non Hodgkin Lymphoma ◽

Multicenter Phase ◽

Mantle Cell

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Successful PBSC Mobilization, Collection, Transplantation and Engraftment after Radioimmunotherapy with Yttrium-90 Ibritumomab Tiuxetan for Non-Hodgkin’s Lymphoma (NHL).

Blood ◽

10.1182/blood.v106.11.5517.5517 ◽

2005 ◽

Vol 106 (11) ◽

pp. 5517-5517 ◽

Cited By ~ 2

Author(s):

Pamela Ely ◽

Diane M. Stearns ◽

Bassem I. Zaki ◽

Thomas F. Fitzmaurice ◽

Marc Gautier ◽

...

Keyword(s):

Follicular Lymphoma ◽

Mantle Cell Lymphoma ◽

Cell Lymphoma ◽

Median Number ◽

Cell Transplant ◽

Ibritumomab Tiuxetan ◽

Autologous Transplant ◽

Cd34 Cells ◽

Mantle Cell ◽

Yttrium 90

Abstract Radioimmunotherapy (RIT) is a useful addition to the armamentarium against NHL. Due to concerns about chronic myelosuppression and the possible inability to mobilize stem cells or tolerate further therapy after RIT, this modality has not been commonly utilized in potential transplant candidates. We report the successful mobilization, collection, transplantation and engraftment of 5 patients with NHL following yttrium-90 ibritumomab tiuxetan. Patients had follicular lymphoma, grade I or II (n=3), transformed follicular lymphoma (n=1) or blastic variant mantle cell lymphoma (n=1). Time from RIT to mobilization was 10 months (median; range 7–27 months). The median number of regimens prior to RIT was 2.5 (range 1–4) including prior autologous transplant (n=1). The median number of regimens following RIT and prior to transplant was 1.5 (range 1–2). All patients exhibited chemosensitive disease. Patients were mobilized with R-ICE/G-CSF (n=4) or G-CSF alone (n=1) and required 2.8 leukaphereses (mean; range 2–5). The CD34 yield was 3.8x106 CD34+ cells/kg (median; range 3.4–5.1x106 CD34+ cells/kg). All patients received busulfan, VP-16, ARA-C and cyclophosphamide (BVAC) as the preparatory regimen. One patient received IL-2 from day 0 to day 11. Time to engraftment was 13 days (median; range 9–19 days) for an absolute neutrophil count (ANC) >500 cells/ml and 23 days (median; range 15–44 days) for a platelet count>20x103/ml. The patient on the IL-2 study showed delayed engraftment of both ANC (day 19) and platelets (day 27). The patient with mantle cell lymphoma, who was undergoing his second autologous transplant, exhibited delayed platelet engraftment (day 44). Time to engraftment did not differ significantly for either ANC (p=0.16) or platelets (p=0.10) in 18 RIT-naïve NHL patients receiving BVAC and an autologous peripheral blood stem cell transplant (PBSC) during the same time period. There were no treatment-related deaths. With a median follow up of 12 months, one patient has died of disease recurrence. Two patients remain in complete remission. Two patients are alive with disease (relapse at 12 months and 14 months) and are currently receiving therapy. No patient has demonstrated laboratory or cytogenetic evidence of a myelodysplastic syndrome. In conclusion, heavily pretreated patients who have received radioimmunotherapy with yttrium-90 ibritumomab tiuxetan and subsequently relapse can successfully undergo mobilization, collection, and autologous PBSC transplant. These patients demonstrate full engraftment, durable remissions and tolerate additional therapy should relapse occur following transplant.

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Phase II Study of Vorinostat for Treatment of Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma and Mantle Cell Lymphoma

Journal of Clinical Oncology ◽

10.1200/jco.2010.32.1398 ◽

2011 ◽

Vol 29 (9) ◽

pp. 1198-1203 ◽

Cited By ~ 143

Author(s):

Mark Kirschbaum ◽

Paul Frankel ◽

Leslie Popplewell ◽

Jasmine Zain ◽

Maria Delioukina ◽

...

Keyword(s):

Mantle Cell Lymphoma ◽

Phase Ii ◽

Phase Ii Study ◽

Cell Lymphoma ◽

Objective Response ◽

Progression Free Survival ◽

Median Number ◽

Open Label ◽

Mantle Cell ◽

Open Label Phase

Purpose We performed a phase II study of oral vorinostat, a histone and protein deacetylase inhibitor, to examine its efficacy and tolerability in patients with relapsed/refractory indolent lymphoma. Patients and Methods In this open label phase II study (NCT00253630), patients with relapsed/refractory follicular lymphoma (FL), marginal zone lymphoma (MZL), or mantle cell lymphoma (MCL), with ≤ 4 prior therapies were eligible. Oral vorinostat was administered at a dose of 200 mg twice daily on days 1 through 14 of a 21-day cycle until progression or unacceptable toxicity. The primary end point was objective response rate (ORR), with secondary end points of progression-free survival (PFS), time to progression, duration of response, safety, and tolerability. Results All 35 eligible patients were evaluable for response. The median number of vorinostat cycles received was nine. ORR was 29% (five complete responses [CR] and five partial responses [PR]). For 17 patients with FL, ORR was 47% (four CR, four PR). There were two of nine responders with MZL (one CR, one PR), and no formal responders among the nine patients with MCL, although one patient maintained stable disease for 26 months. Median PFS was 15.6 months for patients with FL, 5.9 months for MCL, and 18.8 months for MZL. The drug was well-tolerated over long periods of treatment, with the most common grade 3 adverse events being thrombocytopenia, anemia, leucopenia, and fatigue. Conclusion Oral vorinostat is a promising agent in FL and MZL, with an acceptable safety profile. Further studies in combination with other active agents in this setting are warranted.

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