Activity of Yttrium 90 (90Y) Ibritumomab Tiuxetan (Zevalin®) in 22 Patients with Relapsed and Refractory Mantle Cell Lymphoma (MCL).

Abstract Background: The management of MCL is a significant therapeutic challenge, especially in patients with relapsed or refractory disease, who are generally refractory 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 unknown. We report the results of an ongoing 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 >5000/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: Twenty-two patients were enrolled and all qualified for evaluation of treatment response and toxicity. The median age was 67 years (range 51–77), and 18 patients were male. 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). Fourteen patients were previously treated with Hyper-CVAD alternating with MTX/Ara-C, 21 previously received rituximab, and 5 previously received bortezomib. Zevalin treatment was generally well tolerated, with the most common toxicities being hematologic. Objective responses were observed in 8 of 22 patients (36%), including 3 CR and 2 CRu. Seven of the eight responding patients were previously treated with 3 or less treatment regimens, and all responding patients did not have bulky disease, with the largest lesion measuring 3 cm or less. Median time to progression for CR/CRu patients was 6 months. Conclusion: The observed responses to Zevalin in heavily pretreated patients with MCL are promising, but the duration of responses has been short. Furtherinvestigation is warranted after first or second relapse, and in conjunction with front-line therapy.

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

Blood ◽

10.1182/blood.v104.11.2632.2632 ◽

2004 ◽

Vol 104 (11) ◽

pp. 2632-2632 ◽

Cited By ~ 6

Author(s):

Yasuhiro Oki ◽

Barbara Pro ◽

Ebrahim Delpassand ◽

Verushka Ballaster ◽

Peter McLaughlin ◽

...

Keyword(s):

Phase Ii ◽

Cell Lymphoma ◽

Performance Status ◽

B Cell Lymphoma ◽

Ibritumomab Tiuxetan ◽

Minor Response ◽

Median Response ◽

Platelet Counts ◽

Previously Treated ◽

Yttrium 90

Abstract Background: The management of MCL is a significant therapeutic challenge, especially in patients with relapsed or refractory disease, who are generally refractory 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 unknown. We report the results of an ongoing 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 >5000/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: Fifteen patients were enrolled and all qualified for evaluation of treatment response and toxicity. The median age was 64 years (range 51–77), and 13 patients were male. 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). Six of the patients did not respond to their last regimen, while another 6 achieved only a partial response to the last regimen. Ten patients were previously treated with Hyper-CVAD alternating with MTX/Ara-C. Zevalin treatment was generally well tolerated, with the most common toxicities being hematologic. The median times to nadir for platelet and neutrophil counts were 41 days (range 26–63) and 48 days (26–65), respectively. Median durations of platelet (<50,000/mm3) and neutrophil (<1,000/mm3) toxicities were 15 days (range 0–68+) and 0 days (range 0–62), respectively. Three patients required platelet transfusions (range 1–3), and 5 experienced neutrophil toxicity (<1,000/mm3), for which G-CSF was administered until neutrophil recovery. One patient was admitted to the hospital with neutropenic fever and documented stenotrophomonas maltophilia sepsis, which was successfully controlled with IV antibiotics. Objective responses were observed in 5 patients (33%), including 3 CR and 2 CRu. Two additional patients had a minor response, and 1 patient 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. Response was observed in all IPI score groups (0–3). Response rate was higher in patients who had had 1 or 2 prior regimens than in patients with 3 or more prior regimens (67% vs 11%, p<0.001). Median progression free survival for entire group was 4.9 months and median response duration of CR/CRu patients was 5.7 months. At the moment, three patients are free of progression at 123, 200 and 380 days. Conclusion: 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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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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Thiotepa Containing Regimen As Conditioning Chemotherapy for Lymphoma Involving Central Nervous System Compared with BuCyE (Busulfan, Cyclophosphamide and Etoposide)

Blood ◽

10.1182/blood.v124.21.1190.1190 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1190-1190

Author(s):

Yi Rang Kim ◽

Dok Hyun Yoon ◽

Shin Kim ◽

Kyoungmin Lee ◽

Eun Hee Kang ◽

...

Keyword(s):

B Cell ◽

Cell Lymphoma ◽

Performance Status ◽

Primary Cns Lymphoma ◽

B Cell Lymphoma ◽

Cns Lymphoma ◽

Ecog Performance Status ◽

Large B Cell Lymphoma ◽

Conditioning Regimens ◽

Large B Cell

Abstract Aims Primary or secondary central nervous system (CNS) lymphoma is a rare entity which often leads to unsatisfactory outcome. Autologous stem cell transplantation (ASCT) using thiotepa containing regimen as conditioning chemotherapy showed improved outcomes in patients with CNS lymphoma. However, there are insufficient data on response to treatments and safety profile of thiotepa containing regimen in Asian population. We, therefore, aimed to evaluate clinical outcomes including safety profile and response to thiotepa, busulfan and cyclophosphamide (TBC) chemotherapy compared with busulfan, cyclophosphamide and etoposide (BuCyE) as conditioning regimens in patients with CNS lymphoma. Methods From November 2005 to April 2014, patients with primary and secondary CNS lymphoma who underwent one of the two conditioning regimens (TBC or BuCyE) followed by ASCT were included in this retrospective analysis. All patients were less than 66 years of age at the time of ASCT. TBC consists of thiotepa 250 mg/ m2 on day -9 to day -7, busulfan 3.2 mg/kg on day -6 to day-4 and cyclophosphamide 60 mg/kg on day -3 to day -2. BuCyE consists of busulfan 3.2 mg/kg on day -7 to day -5, etoposide 200 mg/m2 twice a day on day -5 to day-4 and cyclophosphamide 50 mg/kg on day -3 and day -2. Patient demographics, ECOG performance status, baseline and follow-up CBC profile, adverse events and radiologic response for 2 years after ASCT were retrospectively reviewed. Response to treatment was assessed by IELSG criteria. Event free survival (EFS), overall survival (OS) and date of engraftment were calculated by Kaplan-Meier method and compared by log-rank test. Adverse events were scored according to National Cancer Institute Common Terminology Criteria of Adverse Event version 4.0. Engraftment was defined as absolute neutrophil count (ANC) > 500 /mm3, and platelet count > 20,000 /mm3. Results Sixty one patients with primary or secondary CNS lymphoma underwent with TBC (n=26) or BuCyE (n=35) as conditioning regimen followed by ASCT. In TBC group, 17 patients (diffuse large B cell lymphoma: 17) had primary CNS lymphoma and 9 patients (diffuse large B cell lymphoma: 7, angioimmunoblastic lymphoma: 1 and T-lymphoblastic lymphoma: 1) had secondary CNS lymphoma. In BuCyE group, 28 patients (diffuse large B cell lymphoma: 27 and peripheral T-cell lymphoma: 1) had primary CNS lymphoma and 7 patients (diffuse large B cell lymphoma: 5, NK-T cell lymphoma: 1 and mantle cell lymphoma: 1) had secondary CNS lymphoma. Median age of TBC group and BuCyE group at ASCT was 52.5 years (range, 18-64 years) and 54 years (range, 26-64 years), respectively. Median ECOG performance status of TBC group and BuCyE group was 1 (range 0-2) and 1 (range 0-1), respectively. After the induction chemotherapy, 11 patients (42.3%) in TBC group and 21 patients (60%) in BuCyE group had already achieved complete remission (CR). In TBC and BuCyE group, CR had been induced in 9 (64.2%) and 11 (78.5%) among patients in partial remission (PR) after ASCT, respectively. With a median follow up period of 8.6 months (range, 0.2 to 18.5 months), 1-year OS rate did not significantly differ between two arms (76.4% in TBC group and 68.6% in BuCyE group, p=0.634). However, 1-year EFS rate was higher in TBC group (72.8%) compared with BuCyE group (45.7%, p=0.034). TBC group achieved ANC engraftment one day earlier compared to BuCyE group (day 8, range 7-12 days vs. day 9, range 7-12 days) (p= 0.011). However, there was no difference in time to engraftment of platelet between TBC group (median 8 days, range 6 to 34 days) and BuCyE group (median 8 days, range 6 to 22 days, p=0.582). Toxicity profiles are summarized in Table 1. Table 1. Toxicity above grade 2 TBC BuCyE p-value Mucositis 92% 14.3% <0.001 Nausea 72% 34.3% 0.004 Vomiting 24% 2.9% 0.017 Diarrhea 84% 25.7% <0.001 AST,ALT elevation 15.4% 2.9% 0.154 Bilirubin elevation 30.8% 5.7% 0.014 Creatinine elevation 7.7% 0% 0.178 Veno-occlusive disease 7.7% 5.7% 1 Bleeding 3.8% 0% 0.426 Conclusions TBC seems to be a feasible conditioning chemotherapy for Korean patients with acceptable toxicity and efficacy. Disclosures No relevant conflicts of interest to declare.

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Impact of Cell-of-Origin on Outcome of Patients With Diffuse Large B-Cell Lymphoma Treated With Uniform R-CHOP Protocol: A Single-Center Retrospective Analysis From North India

Frontiers in Oncology ◽

10.3389/fonc.2021.770747 ◽

2021 ◽

Vol 11 ◽

Author(s):

Ajay Gogia ◽

Sukesh Nair ◽

Shalabh Arora ◽

Lalit Kumar ◽

Atul Sharma ◽

...

Keyword(s):

B Cell ◽

Response Rate ◽

Cell Lymphoma ◽

Performance Status ◽

B Cell Lymphoma ◽

Cell Of Origin ◽

Ecog Performance Status ◽

Bulky Disease ◽

Large B Cell Lymphoma ◽

The Impact

IntroductionThere is a scarcity of data from India on the impact of cell of origin (COO) on outcomes of diffuse large B-cell lymphoma (DLBCL). This study was conducted to evaluate the impact of COO on outcomes of DLBCL patients treated with uniform rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (RCHOP) protocol.Materials and MethodsThis retrospective analysis included patients who received uniform RCHOP chemoimmunotherapy during the study period (2014–2020) at the Department of Medical Oncology at All India Institute of Medical Sciences (AIIMS), New Delhi, India. The patients were classified as germinal center B-cell like (GCB) or activated B-cell (ABC) type using the Hans classification.ResultsFour hundred seventeen patients with median age of 48 years (range, 18–76) and a male-female ratio of 2:1 were included in the analysis. B symptoms and bulky disease were seen in 42.9% and 35.5%. Extranodal involvement was seen in 50.8% of cases. ECOG performance status (0-2) was present in 65%, and 51% presented with advanced disease. GCB subtype was seen in 43%, and 47% were ABC type. Low- and intermediate-risk international prognostic index (IPI) score was seen in 76% of cases. The overall response rate to RCHOP was 85.8%, including a complete response rate of 74.8%. After a median follow-up of 30 months, the 3-year event-free survival (EFS) and overall survival (OS) were 80% and 88%, respectively. The presence of B symptoms and poor ECOG performance status (3-4) was associated with inferior CR rate. Low albumin (p < 0.001), age >60 years (p = 0.001), bulky disease (p < 0.001), and extranodal involvement (p = 0.001) were associated with inferior EFS, whereas a high IPI risk score was associated with an inferior OS (p < 0.001). EFS and OS were not significantly different between the GCB and ABC subtypes. Grade III/IV anemia, neutropenia, and thrombocytopenia were seen in 7.6%, 13.6%, and 2.7% of patients, respectively. Febrile neutropenia was seen in 8.9% of patients, and there were four treatment-related deaths.ConclusionsCell of origin for DLBCL has no impact on CR, EFS, and OS if patients are appropriately treated with standard doses and frequency of RCHOP. RCHOP is well tolerated in our patients, and results are comparable with the Western data.

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Yttrium 90–Labeled Ibritumomab Tiuxetan Radioimmunotherapy Produces High Response Rates and Durable Remissions in Patients with Previously Treated B-Cell Lymphoma

Clinical Lymphoma ◽

10.3816/clm.2004.n.015 ◽

2004 ◽

Vol 5 (2) ◽

pp. 98-101 ◽

Cited By ~ 84

Author(s):

Leo I. Gordon ◽

Thomas Witzig ◽

Arturo Molina ◽

Myron Czuczman ◽

Christos Emmanouilides ◽

...

Keyword(s):

B Cell ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Response Rates ◽

High Response ◽

Ibritumomab Tiuxetan ◽

Previously Treated ◽

Yttrium 90

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R-CHOP in the Treatment of DLBCL: Single Institution Experience from North India.

Blood ◽

10.1182/blood.v106.11.4773.4773 ◽

2005 ◽

Vol 106 (11) ◽

pp. 4773-4773

Author(s):

Ashok K. Vaid ◽

Sachin Gupta ◽

Dinesh C. Doval ◽

Vineet Talwar ◽

Rajeev Gupta ◽

...

Keyword(s):

Performance Status ◽

B Cell Lymphoma ◽

Response Rates ◽

North India ◽

Base Line ◽

Extranodal Involvement ◽

Ecog Performance Status ◽

Chop Regimen ◽

Bulky Disease ◽

2D Echocardiography

Abstract Diffuse large B-cell lymphoma (DLBCL) is the most frequent type of NHL. Different chemotherapy regimens tested in the past showed RR of appx 80% with no improvement in prognosis & OS. CHOP regimen has been the standard treatment for these patients (pts). Rituximab has improved response rates & survival in CD20 positive lymphoma pts, especially elderly (GELA trial: CR 73% vs. 63%). We retrospectively evaluated pts of DLBCL treated with R-CHOP regimen between April 2001 & June 2005. All pts had biopsy and IHC of lymph node/extranodal site, & CT scan of neck, chest, abdomen; BM biopsies; CBC, serum chemistries; 2D echocardiography/MUGA scans. All pts received Rituximab (375mg/m2) & CHOP 3 weekly for a maximum of 8 cycles. Pts who received at least 1 & 3 cycles of R-CHOP were evaluable for toxicity and response respectively. In total, 36 pts were included for analysis. The median age was 53 years, 10/36 pts (27.8%) were >60 years. 25/36 were male (69.4%). ECOG performance status: 0–1 in 30/36, and 2–4 in 6/36. 11/36 had B-symptoms, 16/36 had high LDH, 6/36 had bulky disease. Extranodal involvement was present in 19/36; 10/36 had ≥2 sites of extranodal involvement. Lymph nodal swelling was most common presentation in 24/36 (66.7%), followed by pain 10/36 (27.8%), weight loss 9/36 (25%), fever 7/36 (19.4%), skin nodules 3/36 (8.3%). Extranodal sites were: bone marrow 5/36, bone 4/36, skin 3/36, GIT 3/36, pleural effusion 2/36, lungs 2/36, other soft tissue 2/36, and parotid, nasopharynx, orbit, adrenal, testes, kidneys-1 each. Gallium scan at base line, done in 12/36, was positive in 11 pts (91%). Stage distribution was as follows: stage-I none, stage-II 10/36 (27.8%), stage-III 13/36 (36.1%), stage-IV 13/36 (36.1%). IPI scoring was-low risk 13/36 (36.1), low intermediate 9/36 (25.0%), high intermediate 13/36 (36.1) & high risk 1/36 (2.8%). A total of 199 cycles of R-CHOP were administered with a median of 6 cycles per patient. Of the 33 pts evaluable for response, 22 achieved CR (66.7%), 9 PR (27.3%), 1 each SD & PD. There were 2 treatment related mortalities. Toxicities were: grade III/IV neutropenia in 12/36 (33.3%), thrombocytopenia 4/36 (11.1%), peripheral neuropathy 2/36 (5.6%). Mild hypersensitivity to Rituximab was seen in 2/36 (5.6%) pts. Only 1 patient had cardiac toxicity in form of CHF. Our study showed response rates (94%) and toxicity profile similar to what has been reported in other studies with R-CHOP. The follow-up is too short to evaluate survival rates. Keywords: DLBCL, Rituximab, CHOP.

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Treatment of Diffuse Large B-Cell Lymphoma with Rituximab, Intensive Induction and High-Dose Consolidation: The Final Analysis of the Czech Lymphoma Study Group (CLSG) R-MegaCHOP-ESHAP-BEAM (R-MEB) Trial.

Blood ◽

10.1182/blood.v110.11.21.21 ◽

2007 ◽

Vol 110 (11) ◽

pp. 21-21

Author(s):

Marek Trneny ◽

Robert Pytlik ◽

David Belada ◽

Katerina Kubackova ◽

Ingrid Vasova ◽

...

Keyword(s):

B Cell ◽

Cell Lymphoma ◽

Performance Status ◽

Bone Marrow Involvement ◽

B Cell Lymphoma ◽

High Dose ◽

Cell Transplant ◽

Bulky Disease ◽

Large B Cell Lymphoma ◽

Large B Cell

Abstract Background. Combined immunochemotherapy with CHOP and rituximab have improved the outcome of patients with diffuse large B-cell lymphoma (DLBCL). and related diseases. However, the cure rate of patients with IPI 3–5 or aaIPI 3 is still only about 50% with this regimen. Given the feasibility of previous CLSG regimens based on high-dose CHOP-ESHAP induction and BEAM consolidation, we have conducted a phase II trial combining this approach with rituximab immunotherapy. Patients and methods. Patients aged 18–65 years with DLBCL and age-adjusted IPI (aaIPI) 2–3 were treated with three cycles of high-dose CHOP (MegaCHOP - cyclophosphamide, 3 g/m2, vincristine 2 mg, adriamycin, 75 mg/m2, and prednisone, 300 mg/m2) with G-CSF every 3 weeks, followed by three cycles of ESHAP (etoposide, 240 mg/m2, cisplatin, 100 mg/m2, methylprednisolone, 2000 mg and Ara-C 2000 mg/m2) every 3 weeks. Four to six doses of rituximab 375 mg/m2 were administered on day 1 of each cycle of induction therapy. High-dose therapy (BEAM) followed by autologous stem cell transplant (ASCT) was used as consolidation. Radiotherapy was given to residual masses or sites of bulky disease. Primary endpoint was progression-free survival (PFS), while secondary endpoints were overall survival (OS) and feasibility of the treatment. Results. From April 2002 to October 2006, 105 consecutive patients from 10 centers were recruited. 58% were men and 42% women with median age 46 years (19–63 years). 74% of patients had stage IV disease, 92% had elevated LDH, 53% had performance status >1, 55% had B symptoms and 19% had bone marrow involvement. aaIPI was 2 in 62% of patients and 3 in 38% of patients. 68% of patients received the whole treatment according to the protocol, including ASCT and radiotherapy. Stem cells mobilization according to the protocol was performed in 90% of patients and was successful in 86% of mobilized patients (77% of all patients). 73% of patients ultimately received ASCT (including 3 patients transplanted after ammended treatment) and 51% of patients received planned radiotherapy. Complete remission (CR) was achieved in 83% of all patients and partial remission (PR) in 2%. Early toxic death rate was 6% and 9% patients had primary refractory disease. Of patients who achieved CR or PR, only 6 subsequently relapsed (7%) and two suffered late toxic death (2%). With a median follow-up of 32 months for living patients, the estimated 2-year PFS is 77% and 2-year OS is 81%. Age less than median (46 years) was strongest predictor of favorable outcome (p = 0,00006 for PFS and p = 0,00013 for OS), while there was no effect of stage, LDH, performance status or aaIPI (2-year PFS 79% for aaIPI 2 and 77% for aaIPI 3, 2-year OS 81% for aaIPI 2 and 80% for aaIPI 3). Delivery of ASCT or radiotherapy did not significantly affected PFS in patients who did not suffered early progression or early toxic death, but radiotherapy modestly improved OS of these patients (p = 0,03). Conclusion. R-MEB has proved to be an effective treatment strategy for younger patients with high-risk aggressive B-cell lymphoma. Currently, CLSG is testing whether utilization of early PET scan may decrease toxicity and improve treatment tolerance while maintaining the efficacy of this regimen.

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Radioimmunotherapy (RIT) with 90Y-Ibritumomab Tiuxetan (Zevalin) for the Treatment of Relapsed or Resistant Aggressive Diffuse Large B-Cell Lymphoma (DLBCL) Heavily Pretreated with Rituximab + Chemotherapy: A GIMURELL Experience.

Blood ◽

10.1182/blood.v110.11.4478.4478 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4478-4478 ◽

Cited By ~ 3

Author(s):

Barbara Botto ◽

Marilena Bellò ◽

Giulia Benevolo ◽

Maria Giuseppina Cabras ◽

Claudia Castellino ◽

...

Keyword(s):

De Novo ◽

Cell Lymphoma ◽

Bone Marrow Involvement ◽

B Cell Lymphoma ◽

Aggressive Lymphoma ◽

Ibritumomab Tiuxetan ◽

Large B Cell Lymphoma ◽

Heavily Pretreated ◽

Previously Treated ◽

Grade Iii

Abstract Introduction: The addition of antibody monoclonal anti CD20 Rituximab to CHOP chemotherapy has resulted in improved CR, progression free survival and overall survival rates for patients affected by diffuse large B cell lymphoma. Recently, RIT with Zevalin has been shown effective in the treatment of relapsed refractory elderly DLBCL. We report the results of a study to evaluate the efficacy and safety of Zevalin in relapsed or chemoresistant aggressive lymphoma previously treated with Rituximab. Patients and methods: Elegibility criteria were as follows: age over 18 years, refractory or chemoresistant CD20+ aggressive lymphoma (grade III follicular, PML or DLBCL de novo) WHO performance status of 0 to 2, stage II bulky, III or IV, bone marrow involvement < 25%, written informed consent in accordance with institutional guidelines. All patients were previously treated with Rituximab and almost two lines of chemotherapy. Patients with pre-treatment platelet counts of > 150.000/mm3 received Zevalin at 0.4 mCi/kg whereas those with platelets < 150.000/mm3 received 0.3 mCi/kg. Results: Fourteen patients were treated with RIT: 5 patients were stage II, 3 stage III, 6 stage IV (5 with bone marrow involvement). Six patients had grade III follicular, 4 primary mediastinal and 4 DLBCL de novo. Ten patients received 0.4 mCi/kg and 4 patients 0.3 mCi/kg. Five chemoresistant patients after 2 or more lines chemoimmunotherapy received RIT in combination with BEAM and subsequent autologous stem cell transplantation (ASCT) and 9 patients were treated with Zevalin alone. Two months after RIT we reported CR 4 patients, PR 5 patients and no response/progression 5 patients (ORR 9/14 patients 64%). All 5 patients treated with RIT + BEAM + ASCT achieved a response (CR 2 patients and PR 3 patients ORR 100%). ORR in 9 patients treated with RIT alone was 46% (CR 2 patients and PR 2 patients). No toxic deaths were observed, two patients died of lymphoma (one patients 1 year after Zevalin infusion and the second progressed and died 5 months after RIT). The most common grade 3–4 AE were neutropenia and thrombocytopenia. Discussion: RIT with 90Y-Ibritumomab Tiuxetan is a safe and effective approach for patients affected by aggressive lymphoma and heavily pretreated with Rituximab + chemotherapy. The effective role of RIT alone or in combination with high dose chemotherapy + ASCT as salvage therapy has to be studied in this subset of patients.

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Radioimmunotherapy (RIT) with 90y-Ibritumomab Tiuxetan (Zevalin) in Relapsed or Refractory Aggressive Lymphoma Previously Treated with Rituximab Containing Regimens

Blood ◽

10.1182/blood.v112.11.5014.5014 ◽

2008 ◽

Vol 112 (11) ◽

pp. 5014-5014

Author(s):

Barbara Botto ◽

Marilena Bellò ◽

Annalisa Chiappella ◽

Roberto Passera ◽

Giulia Benevolo ◽

...

Keyword(s):

Bone Marrow ◽

Response Rate ◽

Cell Lymphoma ◽

Bone Marrow Involvement ◽

Single Agent ◽

B Cell Lymphoma ◽

Stage Ii ◽

Aggressive Lymphoma ◽

Ibritumomab Tiuxetan ◽

Previously Treated

Abstract Introduction: The addition of antibody monoclonal anti CD20 Rituximab to CHOP chemotherapy resulted in improved CR, progression free survival and overall survival rates for patients with diffuse large B cell lymphoma (DLBCL). RIT with Zevalin, as single agent, has been shown to be effective in the treatment of relapsed refractory elderly DLBCL, namely in Rituximab naïve patients. However, in patients pretreated with Rituximab the reported response rate was lower. The aim of this study was to evaluate the efficacy and safety of Zevalin in a group of patients with relapsed or refractory aggressive lymphoma, all heavily pretreated with Rituximab containing regimens. Patients and methods: Inclusion criteria were as follows: age over 18 yrs; relapsed or refractory CD20+ aggressive lymphoma (follicular grade IIIb, PML or DLBCL); WHO performance status of 0 to 2; stage II bulky, III or IV; bone marrow involvement <25 %; written informed consent approved in accordance with institutional guidelines. All patients were previously treated with ≥ 2 lines of Rituximab containing regimens. Patients with pre-treatment platelet counts of > 150 × 109/l received Zevalin at 0.4 mCi/kg whereas those with platelets < 150 109/l received 0.3 mCi/kg. Results: 24 patients were treated with RIT. Five patients had stage II, and 19 stage III/IV; bone marrow involvement was present in 11/24. Nine patients had grade IIIb follicular, 14 DLBCL and one mantle cell lymphoma. Eighteen patients received 0.4 mCi/kg and six patients 0.3 mCi/kg. Eleven patients were treated with RIT alone, six received RIT after standard salvage chemoimmunotherapy and seven were treated with RIT in combination with BEAM and subsequent autologous stem cell transplantation (ASCT). Status of disease before Zevalin treatment was: progressive disease (PD) in 14; complete response (CR) and partial response (PR) after salvage chemoimmunotherapy in 4 and 6 patients respectively. All patients in CR before RIT (4/24) maintained a continous CR after treatment. Overall response rate (ORR) after RIT for patients not in CR (20/24) was: 4 patients (20%) achieved a CR, 7 patients (35%) a PR and 9 patients experienced no response/progression (ORR 11/20 patients 55%). Six of seven patients treated with RIT + BEAM + ASCT achieved a response (CR 4 patients and PR 2 patients), one patient progressed immediately after the end of program. ORR in 11 patients treated with RIT alone and in six patients treated with chemotherapy + RIT were 46% and 50% respectively. With a median follow up of 32 months, OS and PFS rates were 67% and 52%. Eight patients died, all because of lymphoma. The most common grade 3–4 adverse events were neutropenia and thrombocytopenia. Discussion: the results of this study suggest that RIT with 90Y-Ibritumomab Tiuxetan is a safe and effective treatment for patients with relapsed/refractory aggressive lymphoma even if they were pretreated with Rituximab containing chemotherapy.

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