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

1992 ◽  
Vol 10 (11) ◽  
pp. 1696-1711 ◽  
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.

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

1996 ◽  
Vol 14 (7) ◽  
pp. 1974-1981 ◽  
Author(s):  
M S Kaminski ◽  
K R Zasadny ◽  
I R Francis ◽  
M C Fenner ◽  
C W Ross ◽  
...  
Keyword(s):  
Complete Remission ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
High Rate ◽  
Whole Body ◽  
Hematologic Toxicity ◽  
Low Grade ◽  
Tracer Dose ◽  
Iodine 131

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.

Combination Therapy Targeting Two Different Antigens with Anti-CD22 Radioimmunotherapy and Anti-CD20 Immunotherapy in Non-Hodgkin Lymphoma (NHL): Phase I Results

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3680-3680 ◽  
Author(s):  
Michael B Tomblyn ◽  
Thomas E. Witzig ◽  
Andrew L Himelstein ◽  
Rebecca Elstrom ◽  
Ebenezer A Kio ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Phase I ◽  
B Cell ◽  
Tumor Targeting ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Therapeutic Activity ◽  
Normal Organ ◽  
Grade 3 ◽  
Anti Cd20

Abstract Abstract 3680 Background: Current NHL radioimmunotherapy is administered with unlabeled antibody targeting the same B-cell antigen. This decreases sequestration of the radiolabeled antibody by normal B-lymphocytes, but potentially blocks access of the radiolabeled antibody to the tumor sites. In clinical studies, yttrium-90 radiolabeled anti-CD22 epratuzumab (90Y-epratuzumab) has demonstrated therapeutic activity with acceptable toxicity when given weekly × 2 at doses up to 20 mCi/m2 (Morschhauser et al., J Clin Oncol. 2010;28:3709–16), while separate studies showed that a 200-mg/m2 dose of anti-CD20 veltuzumab given weekly × 4 readily depletes peripheral blood B-cells and is also therapeutically active (Morschhauser et al., J Clin Oncol, 2009;27:3346–53). In mice bearing human B-cell lymphoma xenografts, this non-competing combination showed improved therapeutic responses over either agent alone (Mattes et al., Clin Cancer Res. 2008;14:6154–60). As such, a multicenter, phase I/II study was undertaken to evaluate combination therapy with 90Y-epratuzumab and veltuzumab. Methods: Adult patients with aggressive NHL who failed ≥ 1 prior standard regimen (excluding autologous SCT) were eligible if they had measurable CT lesions, ECOG 0–1 performance status, <25% bone marrow involvement, hemoglobin ≥ 10 g/dL, ANC ≥ 1.5 × 109/L, platelets ≥ 100 × 109/L and were >4 weeks beyond last treatment. All patients received a 4-week treatment regimen (weekly 200 mg/m2 veltuzumab, 3–5 mCi 111In-epratuzumab on week 2, 90Y-epratuzumab on weeks 3 and 4). Using NCI CTCAE v4.0 toxicity criteria, dose-limiting toxicity (DLT) was defined as Grade 4 hemoglobin, platelet or neutrophil levels >7 days or not recovered to Grade 1 by 12 weeks, or any non-hematologic Grade 3 or 4 events. Starting at 15 mCi/m2, a standard 3+3 dose escalation determined the MTD of 90Y-epratuzumab. Treatment response utilized CT-based 2007 IWG revised criteria. Serial 111In imaging and serum samples were used to assess biodistribution, tumor targeting and determine normal organ radiation dosimetry. ELISA-based assays were used to measure veltuzumab pharmacokinetics and any human anti-veltuzumab antibodies (HAHA). Results: Fifteen patients (10 male/5 female, 56 – 84 years old) with diffuse large B-cell lymphoma (DLBCL N=7), transformed follicular lymphoma (TFL, N=4) or mantle cell lymphoma (MCL, N=4) have now been enrolled. They had 3 median prior treatments (1 – 7) [RCHOP (N=15); bendamustine plus rituximab (N=5); ICE, lenalidomide, bortezomib (N=2 each); others (1 each)] and had low (N=3), low-intermediate (N=3), high-intermediate (N=7), or high (N=2) IPI risk scores. Treatment was well-tolerated with no infusion reactions. 111In-imaging showed normal biodistribution, with acceptable normal organ dosimetry for the scheduled 90Y dose, and tumor targeting occasionally visualized. There was no evidence of HAHA, and the serum clearance of veltuzumab and 111In-epratzumab in combination was comparable to that reported previously for these agents alone. The 90Y dose was repeatedly de-escalated from 15 (N=3) to 12 (N=3), 9 (N=6), and currently 6 (N=3) mCi/m2 due to 7 hematologic DLTs at ≥ 9 mCi/m2in 6 patients involving Grade 3-thrombocytopenia (N=5) or neutropenia (N=2). Clinically, there were 3 SAEs (pneumonia, non-infectious pneumonitis, fracture from fall), but no other major infections or bleeding. Of 11 patients who have now had treatment response assessments, 5 (45%) had objective responses, including one DLCBL patient with a complete response (CR) continuing 12 months later and 4 patients (1 DLBCL, 3 TFL) with partial responses (PRs), with one continuing at 4 weeks and 3 relapsed at 3 – 6 months. Four other patients (1 DLBCL, 3 MCL) achieved stable disease (SD) continuing up to 6 months as best response, resulting in a disease control rate of 82% (CR+PR+SD). Conclusions: Combination treatment was well-tolerated, with the PK behavior of the two agents substantially unchanged, and with initial evidence of therapeutic activity (including one durable CR) in these difficult-to-treat patients. Hematologic toxicity necessitated lowering the 90Y dose, most likely due to the prior aggressive chemotherapies or depletion of the normal sequestering B-cell pool by veltuzumab preceding 90Y-epratzumab. The trial is continuing to determine an acceptable 90Y dose and define the safety and efficacy profile of this combination approach. Disclosures: Sharkey: Immunomedics: Employment. Rojo:Immunomedics: Employment. Wegener:Immunomedics: Employment. Goldenberg:Immunomedics: Employment, Equity Ownership.

Efficacy and Safety of Tositumomab and Iodine-131 Tositumomab (Bexxar) in B-Cell Lymphoma, Progressive After Rituximab

2005 ◽  
Vol 23 (4) ◽  
pp. 712-719 ◽  
Author(s):  
Sandra J. Horning ◽  
Anas Younes ◽  
Vinay Jain ◽  
Stewart Kroll ◽  
Jennifer Lucas ◽  
...  
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Response Duration ◽  
Large Cell ◽  
Complete Response ◽  
Median Number ◽  
Iodine 131 ◽  
Total Body ◽  
Grade 3

Purpose To determine overall response (OR) and complete response (CR) rates, response duration, progression-free (PFS) and overall survival and safety with the tositumomab and iodine-131 tositumomab (131I tositumomab) therapeutic regimen in patients with indolent, follicular large-cell, or transformed B-cell lymphoma, progressive after rituximab. Patients and Methods From July 1998 to November 1999, 40 patients (24 rituximab nonresponders: 11 with response < 6 months, and five with response ≥ 6 months) received a therapeutic dose (0.65 to 0.75 Gy per platelet count) of 131I tositumomab based on total-body dosimetry in this prospective phase II study. The median number of prior treatments was four; 59% of patients were chemotherapy-resistant. Results Confirmed OR (65%) and CR (38%) rates were not significantly associated with prior rituximab response. With a median follow-up of 3.3 years, the median PFS was 10.4 months, 24.5 months for responders, and not reached for CR patients. Among follicular grade 1 or 2 patients with tumors ≤ 7 cm (n = 21), the OR and CR rates were 86% and 57%. Estimated 3-year PFS in this subgroup was 48%, compared with 11% for all others (P = .002). Transient grade 3 to 4 marrow toxicity was seen in 50% of patients. Two patients, one of whom received two subsequent chemotherapy regimens, developed secondary myelodysplasia. Conclusion 131I tositumomab is effective in CD20-positive lymphoma progressive after rituximab, with a 65% OR rate and median PFS of 24.5 months for responders. Patients with follicular grade 1 or 2 histology and tumors ≤ 7 cm achieved very high OR and CR rates, with 48% PFS at 3 years.

Pentostatin, Cyclophosphamide, and Rituximab (PCR) Achieve High Response Rates in Indolent B-Cell Lyphoma without Prolonged Myelosuppression

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 835-835 ◽  
Author(s):  
Felipe Samaniego ◽  
Michelle Fanale ◽  
Barbara Pro ◽  
F.B. Hagemeister ◽  
Peter McLaughlin ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Nucleoside Analog ◽  
Lymphocytic Leukemia ◽  
Lymphoid Cells ◽  
Effective Regimen ◽  
Mixed Response ◽  
Grade 3

Abstract Background: The addition of rituximab to combination chemotherapy has improved treatment outcomes of indolent lymphomas. Combination therapy with purine analogs, akylating agents, and monoclonal antibodies is a promising approach for treating indolent B-cell lymphoma. Nucleoside analog-based regimens selectively target lymphoid cells, making them attractive drugs for lymphoid cancers. Pentostatin is a nucleoside analog that compared with other nucleoside analogs is reported to have less bone marrow cell toxicity. The combination of pentostatin, cyclophosphamide, and rituximab (PCR) is an effective regimen for relapsed chronic lymphocytic leukemia. Methods:In this study, we examined the efficacy of pentostatin, cyclophosphamide, and rituximab for the treatment of B-cell lymphoma. Pentostatin (4 mg/m2), cyclophosphamide (600 mg/m2), and rituximab (375 mg/m2) were given on day 1 of a 21-day cycle with planned 6 or 9 cycles and restaging after every 3 cycles. Patients received prophylaxis with acyclovir 400 mg/po bid and trimethoprim-sulfamethoxazole 3 times per week. Small lymphocytic lymphoma/chronic lymphocytic leukemia (SLL/CLL) tissues were stained for ZAP70 protein. Results: At the time of abstract submission, 80 patients with a median age was 60 years were treated, 43 patients with follicular lymphoma, 27 with SLL/CLL, and 9 with mucosa-associated lymphoid tissue. We observed an overall response of 77 out of 80 (96%), CR/CRu in 65 out of 80 (81%), PR in 12 out of 80 (15%), and mixed response or progression in 3 out of 80 (4%). Neutropenia (49% < 1000/uL), thrombocytopenia (2% < 100,000/uL), nausea (15% grade 3), fatigue (37% grade 3 and 4), and muscle pain (21% grade 3) was observed. ZAP70 staining and response will be reported. Two patients experienced prolonged pancytopenia that resolved and no cases of myelodysplasia were observed. Conclusions: PCR therapy is an effective regimen in indolent B cell lymphoma with tolerable toxicity.

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

Blood ◽  
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 &lt; 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 &lt; 0.001) experienced significantly longer PFS. Patients who achieved CR (p &lt; 0.001) or PR (p = 0.003), received R with every cycle (p &lt; 0.001), received 3 or more cycles (p &lt; 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.

scholarly journals Clinical efficacy and molecular biomarkers in a phase II study of tucidinostat plus R-CHOP in elderly patients with newly diagnosed diffuse large B-cell lymphoma

2020 ◽  
Vol 12 (1) ◽  
Author(s):  
Mu-Chen Zhang ◽  
Ying Fang ◽  
Li Wang ◽  
Shu Cheng ◽  
Di Fu ◽  
...  
Keyword(s):  
Elderly Patients ◽  
B Cell ◽  
Response Rate ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Molecular Biomarkers ◽  
Newly Diagnosed ◽  
Large B Cell Lymphoma ◽  
Grade 3 ◽  
Large B Cell

Abstract Background Elderly patients with diffuse large B-cell lymphoma (DLBCL) present with poor clinical outcome and intolerance to intensive chemotherapy. Histone deacetylase inhibitors (HDACIs) show anti-lymphoma activities and can be applied to treat DLBCL. This study aimed to evaluate efficacy and safety of oral HDACI tucidinostat (formerly known as chidamide) plus R-CHOP (CR-CHOP) in elderly patients with newly diagnosed DLBCL (International Prognostic Index ≥ 2). Results Among 49 patients, the complete response rate was 86%, with overall response rate achieving 94%. The 2-year progression survival (PFS) and overall survival (OS) rates were 68% (95% CI 52–79) and 83% (95% CI 68–91). Comparing with historical control (NCT01852435), the 2-year PFS and OS rates of double-expressor lymphoma phenotype (DEL) were improved, and negative prognostic effect of histone acetyltransferases CREBBP/EP300 mutations was also mitigated by CR-CHOP. Grade 3–4 neutropenia was reported in 171, grade 3–4 thrombocytopenia in 27, and grade 3 anemia in 11 of 283 cycles. No grade 4 non-hematological adverse event was reported. Conclusion CR-CHOP is effective and safe in elderly patients with newly diagnosed DLBCL. Relevance of DEL phenotype and molecular biomarkers on CR-CHOP response warrants further investigation in DLBCL. Trial registration ClinicalTrial.gov, NCT02753647. Registered on April 28, 2016.

scholarly journals Diffuse large B-cell lymphoma of the vagina in pregnancy

2020 ◽  
Vol 13 (1) ◽  
pp. e233145
Author(s):  
Nwabundo Anusim ◽  
Filip Ionescu ◽  
Olabisi Afolayan-Oloye ◽  
Susanna S Gaikazian
Keyword(s):  
B Cell ◽  
Cell Lymphoma ◽  
Cardiac Activity ◽  
Pelvic Mass ◽  
B Cell Lymphoma ◽  
Whole Body ◽  
Rare Presentation ◽  
Whole Body Mri ◽  
Large B Cell Lymphoma ◽  
Large B Cell

A 28-year-old primigravida was evaluated for complaints of difficulty urinating and pelvic pain of 6-weeks duration. She denied fever, night sweats, weight loss or fatigue. Pelvic ultrasonography revealed a single fetal pole with cardiac activity and a 7 cm mass in the anterior vagina which encased the urethra. The diagnosis of diffuse large B-cell lymphoma germinal centre type was made on analysis of biopsied pelvic mass. Whole body MRI revealed the disease was limited to the vagina. The patient received six cycles of Rituximab-cyclophosphamide, doxorubicin, vincristine and prednisone with significant improvement in her symptoms. Serial ultrasounds over the subsequent months showed appropriate development of the fetus. Whole body MRI after treatment showed decreased size and decreased signal of the primary pelvic mass compatible with favourable treatment response. Challenges in the management of this rare presentation of lymphoma are discussed.

scholarly journals Parsaclisib, a potent and highly selective PI3Kδ inhibitor, in patients with relapsed or refractory B-cell malignancies

Blood ◽  
2019 ◽  
Vol 133 (16) ◽  
pp. 1742-1752 ◽  
Author(s):  
Andres Forero-Torres ◽  
Radhakrishnan Ramchandren ◽  
Abdulraheem Yacoub ◽  
Michael S. Wertheim ◽  
William J. Edenfield ◽  
...  
Keyword(s):  
Respiratory Failure ◽  
B Cell ◽  
Cell Lymphoma ◽  
Phase 1 ◽  
Objective Response ◽  
B Cell Lymphoma ◽  
Janus Kinase ◽  
B Cell Malignancies ◽  
Once Daily ◽  
Grade 3

Abstract This phase 1/2 study assessed parsaclisib (INCB050465), a next-generation, potent, and highly selective phosphatidylinositol 3-kinase δ (PI3Kδ) inhibitor, in patients with relapsed or refractory B-cell malignancies, alone or in combination with a Janus kinase 1 inhibitor (itacitinib) or chemotherapy (rituximab, ifosfamide, carboplatin, and etoposide). Seventy-two patients received parsaclisib monotherapy (5-45 mg once daily). Expansion doses were 20 and 30 mg once daily; intermittent dosing at 20 mg (once daily for 9 weeks, then once weekly) was explored. No dose-limiting toxicities were identified, and maximum tolerated dose was not reached. Most common nonhematologic treatment-emergent adverse events (TEAEs) were diarrhea/colitis (36%), nausea (36%), fatigue (31%), and rash (31%). Grade 3/4 neutropenia occurred in 19% of patients. Serious TEAEs (&gt;2 patients) were diarrhea/colitis (n = 9), pyrexia (n = 4), hypotension (n = 3), and sepsis (n = 3). Aspartate and alanine transaminase elevations occurring before treatment discontinuation were grade 1, except 1 grade 3 event each, secondary to sepsis. Two patients experienced 3 fatal parsaclisib-unrelated TEAEs (respiratory failure; respiratory failure and sepsis). In non-Hodgkin lymphoma (NHL), objective response rates to monotherapy were 71% in follicular lymphoma, 78% in marginal zone lymphoma, 67% in mantle cell lymphoma, and 30% in diffuse large B-cell lymphoma; 93% of responses occurred at first assessment (∼9 weeks). Parsaclisib has demonstrated antitumor activity in relapsed or refractory B-cell NHL with the potential for improved long-term patient outcomes. Phase 2 studies in relapsed or refractory B-cell NHL subtypes are ongoing. This trial was registered at www.clinicaltrials.gov as #NCT02018861.

Immunoglobulin G Fc Polymorphism Is Correlated with Rituximab-Induced Neutropenia Following Autologous Hematopoietic Cell Transplantation.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 442-442
Author(s):  
Wen-Kai Weng ◽  
Sandra J. Horning ◽  
Robert S. Negrin ◽  
Ronald Levy
Keyword(s):  
B Cell ◽  
Cell Transplantation ◽  
Hematopoietic Cell Transplantation ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Hematopoietic Cell ◽  
Cell Depletion ◽  
B Cell Depletion ◽  
Grade 3 ◽  
Autologous Hematopoietic Cell Transplantation

Abstract Rituximab has been given following autologous hematopoietic cell transplantation (HCT) for recurrent or refractory B cell lymphoma with the goal of eradicating minimal residual disease. Our recent study showed that this is a feasible strategy although transient grade 3 or 4 neutropenia was observed in 51% of patients (Blood 103:777, 2004). We also reported that two IgG Fc receptor (FcγR) polymorphisms, FcγRIIIa 158 V/V and FcγRIIa 131 H/H genotypes, predict response to rituximab therapy in patients with follicular lymphoma, probably due to their role in the antibody-dependent cellular cytotoxicity (ADCC) (JCO 21:3940, 2003). In the current report, we correlated FcγR polymorphisms with clinical outcomes after post-transplant rituximab. A total of 35 patients with diffuse large cell (25 patients), mantle cell (3 patients), transformed (3 patients) or other (4 patients) subtypes of B cell lymphoma received high-dose therapy, autologous HCT and rituximab, administrated as 4-weekly infusions (375 mg/m2) starting around day 42 and 6 months after HCT. Genomic DNA was available for FcγR polymorphism analysis in 33 cases. For the FcγRIIIa polymorphism, 4 (12%) patients were homozygous valine/valine (158 V/V), 14 (42%) patients were heterozygous valine/phenylalanine (158 V/F) and 15 (46%) patients were homozygous phenylalanine/phenylalanine (158 F/F). For the FcγRIIa polymorphism, 8 (24%) patients were homozygous histidine/histidine (131 H/H), 16 (49%) patients were heterozygous histidine/arginine (131 H/R) and 9 (27%) patients were homozygous arginine/arginine (131 R/R). We did not find a correlation of either the FcγRIIIa V/F polymorphism or the FcγRIIa H/R polymorphism with time to relapse after HCT. But the small number of relapses limited our power. Although rituximab infusions were well tolerated in this group of patients, 32% of the treatment courses in this study were associated with rituximab-induced grade 3 or grade 4 neutropenia (ANC &lt; 1000/μl), which was recorded in 51% of patients. These neutropenic episodes were not associated with infection and responded well to G-CSF treatment. The reason for this high incidence of rituximab-induced neutropenia is unclear. Among the 33 patients analyzed for FcγR polymorphisms, FcγRIIIa 158 V/V homozygotes experienced relatively greater neutropenia (V/V : 3/4, 75%; V/F: 8/14, 57%; F/F: 5/15, 33%). For the 57 treatment courses, the FcγRIIIa 158 V/V genotype was associated with a greater chance of rituximab-induced neutropenia, compared to F carriers (158 V/F and 158 F/F). The incidence of rituximab-induced neutropenia was 71% for V/V, 39% for V/F, 19% for F/F and 28% for F carriers (V/V vs F carriers, p = 0.035). In contrast, the FcγRIIa H/R polymorphism had no impact on rituximab-induced neutropenia. Although the mechanism of rituximab-induced neutropenia is unknown, this report implicates an FcγR-mediated process, such as ADCC. It is possible that B cell depletion by rituximab affects either directly or indirectly cytokine (e.g. G-CSF) production as a mechanism for neutropenia. It will be of great interest to study the correlation between FcγR polymorphisms and the prevalence and duration of B cell depletion after rituximab therapy in larger clinical studies both after HCT and in conjunction with other myelosupressive therapies.

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