Tandem HD-chemotherapy and myeloablative radioimmunotherapy with 131I-anti-CD20 rituximab in relapsed and refractory B-cell lymphoma: Results of a phase II study of the German RAIT Study Group

13007 Background: Radioimmunotherapy has been shown to be effective in CD20 + B-cell lymphomas. Both non-myeloablative as well as myeloablative regimens have been employed for low grade and high grade lymphomas with impressive response rates and remission durations. Recently, the Press group and our group published data on myeloablative 131-I-anti-CD20 RAIT with high response rates and favourable long term survival especially in follicular lymphomas and transformed FL. Therefore, a phase II study is currently being done within the German Radioimmunotherapy Group, interim analysis data are presented. Methods: Patients were to receive R-Dexa-BEAM, followed by BEAM and HD-RAIT 2–6 months after BEAM. 131-I-Rituximab was administered with a maximum kidney and lung dose of 25 Gy. Sample size was calculated to be 16 to evaluate toxicity and feasibility of the tandem approach as primary endpoint. Results: 16 pts with relapsed (14) or primary refractory (2) B-cell lymphomas (FLI,II: 4pts; DLBCL: 4pts (all early relapses); transformed FL: 6 pts; MCL:1 pt, marginal zone lymphoma: 1 pt) were treated with 1 (15 pts) or 2 cycles (1 pt) of R-Dexa-BEAM. 13/16 pts achieving PR (5) or CRu (8) were treated with BEAM, 2 pts with PD and 1 with subdural hematoma were drop outs. After BEAM, 9/13 pts were in CR, 3/13 PR, 1/13 PD. Of 12 responding pts, 6 received HD-RAIT (1 pancytopenia, 1 hepatic, 2 pulmonary toxicity, 3 too early). After HD RAIT, 5/6 pts were in CR, 1 in PR. 4/6 pts (3 CR, 1 PR) are alive for 22–31 months, 2 pts died in CR, 1 of interstitial lung disease 2 months after HD-RAIT, 1 pt of pneumonia 8 months after HD-RAIT. Conclusions: Myeloablative RAIT is a feasible and effective treatment modality for relapsed poor prognosis CD20+ B-NHL not having severe toxicity due to the salvage regimen and HD-chemotherapy. HD RAIT offers the potential for long term relapse free survival. Final analysis of toxicity and outcome of this phase II study will be presented at the meeting. No significant financial relationships to disclose.

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LONG‐TERM ANALYSES FROM L‐MIND, A PHASE II STUDY OF TAFASITAMAB PLUS LENALIDOMIDE (LEN) IN PATIENTS (PTS) WITH RELAPSED OR REFRACTORY DIFFUSE LARGE B‐CELL LYMPHOMA (R/R DLBCL)

Hematological Oncology ◽

10.1002/hon.28_2879 ◽

2021 ◽

Vol 39 (S2) ◽

Author(s):

J Duell ◽

K. J Maddocks ◽

E González‐Barca ◽

W Jurczak ◽

A. M Liberati ◽

...

Keyword(s):

B Cell ◽

Phase Ii ◽

Phase Ii Study ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Large B Cell Lymphoma ◽

Large B Cell

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Long-term results of the R-CEOP90 in the treatment of young patients with chemotherapy-naïve diffuse large B cell lymphoma: A phase II study

Leukemia & Lymphoma ◽

10.3109/10428194.2013.876632 ◽

2014 ◽

Vol 55 (10) ◽

pp. 2387-2388 ◽

Cited By ~ 2

Author(s):

Qi-Chun Cai ◽

Yan Gao ◽

Xiao-Xiao Wang ◽

Qing-Qing Cai ◽

Ze-Xiao Lin ◽

...

Keyword(s):

B Cell ◽

Phase Ii ◽

Phase Ii Study ◽

Cell Lymphoma ◽

Young Patients ◽

B Cell Lymphoma ◽

Long Term Results ◽

Large B Cell Lymphoma ◽

Large B Cell

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Phase II study of intensified rituximab induction and maintenance for low grade B cell lymphoma

Leukemia & Lymphoma ◽

10.1080/10428194.2017.1319054 ◽

2017 ◽

Vol 58 (12) ◽

pp. 2845-2851

Author(s):

Hirokazu Nagai ◽

Takeshi Shimomura ◽

Makoto Takeuchi ◽

Shuichi Hanada ◽

Takuya Komeno ◽

...

Keyword(s):

B Cell ◽

Phase Ii ◽

Phase Ii Study ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Low Grade

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Augmenting Neutrophil Function By Administration of Peg-Filgrastim Potentiates Rituximab and Is Safe in Patients with Indolent B-Cell Non-Hodgkin Lymphomas: Results of a Phase II Study

Blood ◽

10.1182/blood.v126.23.3975.3975 ◽

2015 ◽

Vol 126 (23) ◽

pp. 3975-3975

Author(s):

Pallawi Torka ◽

Priyank P. Patel ◽

Wei Tan ◽

Gregory Wilding ◽

Seema A. Bhat ◽

...

Keyword(s):

Immune System ◽

B Cell ◽

Phase Ii ◽

Oxidative Burst ◽

Phase Ii Study ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Neutrophil Function ◽

Advisory Board ◽

Low Grade

Abstract Background: Pre-clinical studies have shown that host immune system activation by G-CSF/GM-CSF enhances the biologic activity of rituximab through up-regulation of CD11b/18 expression on neutrophils, increase in the number of circulating granulocytes and higher CD20 epitope density on tumor cells. To further explore the role of augmenting neutrophil function in B-cell lymphoma, we conducted an open-label, single-arm, phase II study evaluating the safety and clinical efficacy of peg-filgrastim and rituximab in patients with low-grade CD20 positive B-cell Non-Hodgkin lymphomas (B-NHL) [chronic lymphocytic leukemia (CLL), follicular lymphoma (FL) and marginal zone lymphoma (MZL)]. (NCT01682044) Materials and methods: Twenty patients with untreated or relapsed/refractory indolent lymphoma were treated with rituximab (375 mg/m2) every other week for 4 doses, and after 8 weeks every 2 months for 4 additional doses (total 8 doses). Peg-filgrastim (6mg) was administered subcutaneously 3 days before each dose of rituximab. Clinical responses and tolerability were examined according to standard international criteria. Biologic monitoring included evaluation of phenotype characteristics of host neutrophils, changes in oxidative burst, and in vitro functional assays including CMC and ADCC at baseline and before each dose of rituximab. Results: Baseline patient characteristics were as follows: Median age: 64 (28-86) yrs; 70% male; FL: 70%, CLL: 20%, MZL: 10%; Ann-Arbor stage- II- 10%, III- 30% and IV- 60%; disease status- newly diagnosed: 1, rituximab refractory: 2, relapsed ≥1 line of therapies: 17. Median number of prior therapies was 2 (1-5); 75% had previously received rituximab and 90% had received prior anti-CD20 monoclonal antibody therapy. The addition of peg-filgrastim to rituximab was well tolerated, and did not increase the frequency or severity of rituximab-related toxicities. Most of the adverse events were grade 1-2 infusion-related toxicities. One patient developed grade 4 hyperuricemia. One patient with MZL died while on treatment due to disease progression. The overall response rate (ORR) was 60% (12/20) with a complete response (CR) rate of 35% (7/20). Median progression-free survival (PFS) was 17.9 months (95% CI- 9.9-27.6 months); median overall survival (OS) was not reached. A shorter time-to-peak oxidative burst after first dose of peg-filgrastim was associated with higher rates of CR (p= 0.04) and longer PFS (p=0.03, figure 1). Though intensity of peak oxidative burst did not correlate statistically with outcomes, patients who achieved CR (and OR) had consistently higher free radical levels compared to those who did not, especially during the first 2 months of treatment. This trend waned during the latter part of therapy suggesting neutrophil exhaustion. Further analyses are ongoing to evaluate the association between rituximab ex vivo immunological assays and clinical endpoints outcomes. Conclusion: The combination of peg-filgrastim and rituximab was well tolerated with favorable response rates and PFS compared to historical controls treated with single-agent rituximab. Augmented neutrophil function was associated with higher CR rates and OS. Our results support further evaluation of strategies that enhance the innate immune system to improve rituximab activity in B-cell lymphoma. Disclosures Off Label Use: Pegfilgrastim has been combined with rituximab in this phase 2 study for treatment of indolent B-cell Non-Hodgkin lymphoma.. Czuczman:Celgene: Employment; Immunogen: Other: Advisory board; MorphoSys: Consultancy; Boehringer-Ingelheim: Other: Advisory Board.

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