Iodine-131-anti-B1 radioimmunotherapy for B-cell lymphoma.

PURPOSE The CD20 B-lymphocyte surface antigen expressed by B-cell lymphomas is an attractive target for radioimmunotherapy, treatment using radiolabeled antibodies. We conducted a phase I dose-escalation trial to assess the toxicity, tumor targeting, and efficacy of nonmyeloablative doses of an anti-CD20 monoclonal antibody (anti-B1) labeled with iodine-131 (131I) in 34 patients with B-cell lymphoma who had failed chemotherapy. PATIENTS AND METHODS Patients were first given tracelabeled doses of 131I-labeled anti-B1 (15 to 20 mg, 5 mCi) to assess radiolabeled antibody biodistribution, and then a radioimmunotherapeutic dose (15 to 20 mg) labeled with a quantity of 131I that would deliver a specified centigray dose of whole-body radiation predicted by the tracer dose. Whole-body radiation doses were escalated from 25 to 85 cGy in sequential groups of patients in 10-cGy increments. To evaluate if radiolabeled antibody biodistribution could be optimized, initial patients were given one or two additional tracer doses on successive weeks, each dose preceded by an infusion of 135 mg of unlabeled anti-B1 one week and 685 mg the next. The unlabeled antibody dose resulting in the most optimal tracer biodistribution was also given before the radioimmunotherapeutic dose. Later patients were given a single tracer dose and radioimmunotherapeutic dose preceded by infusion of 685 mg of unlabeled anti-B1. RESULTS Treatment was well tolerated. Hematologic toxicity was dose-limiting, and 75 cGy was established as the maximally tolerated whole-body radiation dose. Twenty-eight patients received radioimmunotherapeutic doses of 34 to 161 mCi, resulting in complete remission in 14 patients and a partial response in eight. All 13 patients with low-grade lymphoma responded, and 10 achieved a complete remission. Six of eight patients with transformed lymphoma responded. Thirteen of 19 patients whose disease was resistant to their last course of chemotherapy and all patients with chemotherapy-sensitive disease responded. The median duration of complete remission exceeds 16.5 months. Six patients remain in complete remission 16 to 31 months after treatment. CONCLUSION Nonmyeloablative radioimmunotherapy with 131I-anti-B1 is associated with a high rate of durable remissions in patients with B-cell lymphoma refractory to chemotherapy.

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Imaging, dosimetry, and radioimmunotherapy with iodine 131-labeled anti-CD37 antibody in B-cell lymphoma.

Journal of Clinical Oncology ◽

10.1200/jco.1992.10.11.1696 ◽

1992 ◽

Vol 10 (11) ◽

pp. 1696-1711 ◽

Cited By ~ 100

Author(s):

M S Kaminski ◽

L M Fig ◽

K R Zasadny ◽

K F Koral ◽

R B DelRosario ◽

...

Keyword(s):

B Cell ◽

Tumor Targeting ◽

Tumor Imaging ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Whole Body ◽

Tracer Dose ◽

Mixed Response ◽

Iodine 131 ◽

Grade 3

PURPOSE This study was undertaken to evaluate the tumor targeting, toxicity, and therapeutic potential of the anti-B-cell-reactive monoclonal antibody MB-1 (anti-CD37) labeled with iodine 131 given in a nonmarrow ablative dose range in B-cell lymphoma patients who relapsed after chemotherapy. PATIENTS AND METHODS Twelve patients with MB-1-reactive tumors were infused first with 40 mg of trace-labeled (3 to 7 mCi) MB-1. Ten patients who had no serious toxicity postinfusion and who had successful tumor imaging on serial gamma scans then received at least one 40-mg radioimmunotherapy (RIT) dose (25 to 161 mCi). Tracer estimates of delivered whole-body dose (WBD) were used in prescribing a millicurie RIT dose for seven patients. RESULTS Eleven patients had positive tumor imaging after a tracer dose, including patients with bulky tumors and/or large tumor burdens (> or = 1 kg) +/- splenomegaly. However, overall sensitivity for the detection of known tumor sites was only 39%. In six of eight patients with dose-assessable tumors, the radiation dose to at least one tumor was 1.1 to 3.1 times higher than to any normal organ, excluding the spleen for a 40-mg tracer dose. Tracer-dose toxicities included reversible glossal edema in one patient, grade 3 hepatic transaminasemia in another, and early drops in both circulating B and T cells (with decreases in B cells more pronounced) in nearly all patients. RIT toxicity was primarily myelosuppression (especially thrombocytopenia), which had a delayed onset and protracted recovery (without significant recovery until at least 2 months post-RIT). Grade 3 myelosuppression in two of two patients who were treated at a tracer-projected 50-cGy WBD level (133 and 149 mCi) precluded further planned RIT dose escalation. Less myelosuppression was generally observed in patients who were treated at < or = 40-cGy WBD levels. Antimouse antibodies developed in two patients. Six patients had tumor responses post-RIT. Four had responses that lasted more than 1 month (2 to 6 months), which included one complete response, one partial response, one minor response, and one mixed response. Responses seemed to occur more frequently in imaged tumors than in nonimaged tumors. The most durable response occurred in a patient who had the best antibody targeting to tumor. CONCLUSIONS Although 131I-MB-1 has limited diagnostic value, it can produce tumor responses at nonmarrow ablative RIT doses. Further studies that focus on improving tumor targeting with this or other B-cell-reactive radiolabeled antibodies and on ameliorating the myelosuppression associated with the RIT-dosing approach used in this trial are warranted.

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Phase 1/2 study of fractionated 131I-rituximab in low-grade B-cell lymphoma: the effect of prior rituximab dosing and tumor burden on subsequent radioimmunotherapy

Blood ◽

10.1182/blood-2008-08-175653 ◽

2009 ◽

Vol 113 (7) ◽

pp. 1412-1421 ◽

Cited By ~ 57

Author(s):

Tim M. Illidge ◽

Mike Bayne ◽

Nicholas S. Brown ◽

Samantha Chilton ◽

Mark S. Cragg ◽

...

Keyword(s):

B Cell ◽

Induction Therapy ◽

Half Life ◽

Response Rate ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Whole Body ◽

Hematologic Toxicity ◽

Low Grade ◽

Multiple Doses

Abstract The effect of induction therapy with multiple doses of rituximab on the subsequent efficacy and toxicity of anti-CD20 radioimmunotherapy is unknown. We evaluated a novel protocol using 4 weekly infusions of 375 mg/m2 rituximab followed by 2 fractions of 131I-rituximab, preceded by a 100-mg/m2 predose of rituximab, in relapsed indolent B-cell lymphoma. Induction therapy with rituximab significantly increased the effective half-life of 131I-rituximab (P = .003) and high serum levels of rituximab after induction therapy correlated with increased effective half-life of the radioimmunoconjugate (P = .009). Patients with large tumor burdens experienced significant increases in the effective half-life of 131I-rituximab between delivery of the first and second fractions (P = .007). Induction therapy with multiple doses of rituximab did not appear to compromise the clinical efficacy or increase toxicity of subsequent 131I-rituximab radioimmunotherapy. The overall response rate was 94%, with complete response rate 50%. The median time to progression was 20 months, significantly longer than for the last qualifying chemotherapy (P = .001). Fractionation of 131I-rituximab allowed cumulative whole-body doses of more than 120 cGy, approximately 60% greater than those previously achieved with a single administration of a murine radioimmunconjugate, to be delivered without significant hematologic toxicity.

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Development of early gastric cancer 4 and 5 years after complete remission of Helicobacter pylori associated gastric low grade marginal zone B cell lymphoma of MALT type

World Journal of Gastroenterology ◽

10.3748/wjg.v7.i2.248 ◽

2001 ◽

Vol 7 (2) ◽

pp. 248 ◽

Cited By ~ 53

Author(s):

Andrea Morgner

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Early Gastric Cancer ◽

Complete Remission ◽

B Cell ◽

Marginal Zone ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Low Grade

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IVAC +/- R for Relapsed or Refractory B-Cell Non-Hodgkin Lymphomas: Real-World Experience in the Modern Era

Blood ◽

10.1182/blood-2020-134607 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 10-10

Author(s):

Michael J Buege ◽

Phuong H Dao ◽

Esther Drill ◽

Andréa C LeVoir ◽

Terry Pak ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Board Of Directors ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Hematologic Toxicity ◽

Low Grade ◽

Advisory Committees ◽

Prophylactic Measures ◽

Grade 3

Introduction Part B of the modified Magrath regimen (ifosfamide, etoposide, and cytarabine; IVAC) with or without rituximab (R) is utilized as a standalone regimen in the management of relapsed/refractory Burkitt lymphoma and other non-Hodgkin lymphomas (NHL). There are no comparative or prospective data and a paucity of retrospective, non-comparative data to support use of this regimen. A small retrospective study described second-line IVAC use without R in a mixed cohort of patients with diffuse large B-cell lymphoma (DLBCL) or peripheral T-cell lymphoma, suggesting utility as a bridge to hematopoietic cell transplantation (HCT) (Pereira J, et al. Leuk Res. 2006 Jun;30(6):681-5). The activity of this regimen in B-cell NHL, particularly in conjunction with R, and its toxicity remain incompletely described. In this study, we describe our institutional experience with IVAC +/- R in relapsed/refractory B-cell NHL. Methods We reviewed all patients with relapsed/refractory B-cell NHL treated with IVAC +/- R between 1 January 2004 and 30 September 2019 at Memorial Sloan Kettering Cancer Center to assess efficacy and toxicity. Patients who received IVAC as part of sequential or alternating chemotherapy were excluded. Standard dosing consisted of ifosfamide 1500mg/m2 IV over 60min days 1-5, etoposide 60mg/m2 IV over 60min days 1-5, cytarabine 2000mg/m2 IV over 3 hours every 12 hours days 1-2, with or without rituximab 375mg/m2 IV day 0 or 1 in 21- to 28-day cycles (Lacasce A, et al. Leuk Lymphoma. 2004 Apr;45(4):761-7). Results Cohort and treatment characteristics are described in Table 1. Among 54 eligible patients (median age 51 years), 76% had DLBCL; 30% had lymphomatous central nervous system involvement at the time of initiating IVAC. Patients had received median 2 prior lines of therapy, with the last dose of the most recent line of therapy administered a median of 3 weeks prior to initiating IVAC. Patients received median 2 cycles of IVAC +/- R; 48% received IVAC-R. Prophylactic antimicrobials with cycle 1 were utilized in 94%. Most patients received herpesvirus- (81%) and Pneumocystis- (80%) directed prophylaxis; broad-spectrum prophylaxis with a fluoroquinolone was less common (24%). Primary granulocyte colony stimulating factor (GCSF) was utilized in 93% of patients with cycle 1; primary or secondary GCSF was utilized in 94% of cycles. Efficacy outcomes are described in Table 1. Objective response rate (ORR) among 46 evaluated patients was 48%; 17% achieved CR. ORR did not vary significantly between patients who did or did not receive R (58% vs 42%; p = 0.5) but was associated with number of IVAC cycles administered (among responders, 69% received 3-4 cycles while 31% received 1-2 cycles; p < 0.001). At median follow-up of 22 months, median progression-free survival (PFS) and overall survival (OS) were 3.1 months and 4.9 months, respectively (Figure). In Cox proportional hazard regression analysis of survival, patients who received R with every cycle (p = 0.025) and received 3 or more cycles (p < 0.001) experienced significantly longer PFS. Patients who achieved CR (p < 0.001) or PR (p = 0.003), received R with every cycle (p < 0.001), received 3 or more cycles (p < 0.001), or underwent subsequent HCT or CAR-T cell therapy (p = 0.001) experienced significantly longer OS. Toxicity outcomes are described in Table 2. Grade ≥ 3 anemia (93%), neutropenia (94%), and thrombocytopenia (100%; all grade 4) were common, regardless of number of cycles received. Febrile neutropenia (FN) occurred in 65% of patients and complicated 47% of cycles; documented infection occurred in 44%. Risk of FN and infection did not appear to be influenced by use of antimicrobial or GCSF prophylaxis. Grade ≥ 3 elevations in AST/ALT or total bilirubin were uncommon (5.6% and 9.3%, respectively). Neurotoxicity attributed to cytarabine or ifosfamide occurred in 17% of patients and was usually low-grade; hemorrhagic cystitis occurred in one patient. In patients for whom cause of death was documented (n = 37), mortality was attributed to a treatment-related complication in 19%. Conclusion IVAC-R may be a useful bridging therapy for patients with relapsed/refractory B-cell NHL who are planned for HCT. However, its potential for profound hematologic toxicity and life-threatening complications despite prophylactic measures requires careful consideration of less toxic alternatives. Disclosures Straus: Elsevier: Membership on an entity's Board of Directors or advisory committees, Other: CME writer; Targeted Oncology: Consultancy, Speakers Bureau; Imedex, Inc.: Speakers Bureau; NY Lymphoma Rounds: Consultancy; Takeda Pharmaceuticals: Research Funding, Speakers Bureau; Karyopharm Therapeutics: Membership on an entity's Board of Directors or advisory committees; OncLive: Speakers Bureau; ASH: Other: Conference in December 2019 on HL to other physicians during ASH; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees.

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