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R) lymphoma in the rituximab (R) era
Abstracts
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3218 POSTER PACEBOM in relapsed/refractory (R/R) lymphoma in the rituximab (R) era B. Tamjid1 , J. McKendrick2 , R. Doig2 , P. Hosking3 , P. James2 , S. Anthony2 , E. Hawkes2 . 1 Austin Hospital, Medical Oncology, Heidelberg Melbourne, Australia; 2 Eastern Health, Medical Oncology, Melbourne, Australia; 3 Eastern Health, Pathology, Melbourne, Australia Background: R/R lymphoma outcomes are poor. There is no standard treatment. PACEBOM has efficacy for several lymphoma subtypes however most published reports are the 1990’s, prior to routine R for B-cell lymphoma. We evaluate PACEBOM+/-R for R/R lymphoma in this millennium. Methods: In this retrospective, single-centre study, R/R lymphoma patients who received PACEBOM (prednisolone, doxorubicin, cyclophosphamide, etoposide, bleomycin, vincristine, methotrexate) were identified from the pharmacy database. Demographic, treatment, toxicity and survival data were collected. The study was approved by the local IRB. Results: 69 eligible pts were identified. 56/69 were male. Median age was 56.5 yrs. Histological subtypes included 20 DLBCL, 18 FL, 10 TCL, 7 HL, 14 other indolent subtypes. 46(67%) received 2nd line PACEBOM, 23(33%) had 2 prior regimens. 48/52 B-cell NHL had prior R. Median number of cycles was 6 (range 1−6). 29/69 received R-PACEBOM. Overall response rate (ORR) was 72%, 75% in pts who received prior R, and 80% in the R-PACEBOM cohort. 15 pts underwent ASCT post-PACEBOM. Median follow-up was 57 months (m) (3–201). Median PFS & OS post-PACEBOM was 12.4m (range 0−89) & 20.6m(range 0−89). In B-cell NHL pts who had prior R, PFS & OS were improved with R-PACEBOM vs PACEBOM alone (PFS 18m vs 11m, OS not reached vs 16.3m). Most common grade3−4 toxicities were neutropenia (41%), anaemia (16%) & thrombocytopaenia (13%). No difference in toxicity was seen between patients who received R vs no R. Conclusion: PACEBOM is active across all R/R lymphoma subtypes with manageable toxicity and can be safely combined with R. Outcomes were similar to reports of other salvage regimens. PACEBOM remains a suitable option for R/R lymphoma, in pts exposed to prior R & planned for ASCT. Table: ORR by subtype Subtype
ORR, n/N (%)
All DLBCL HL TCL Other indolent lymphomas
50/69 (72%) 13/20 (65) 5/7 (71) 7/10 (70) 25/32 (78)
No conflict of interest. 3219 POSTER 90Y-ibritumomab-tiuxetan consolidation for advanced stage mantle cell lymphoma after first line autologous stem cell transplantation: Is it time for a step forward? P. Mondello1 , N. Steiner2 , S. Cuzzocrea3 , W. Willenbacher2 , C. Arrigo1 , V. Pitini1 , M. Mian4 . 1 Policlinico Universitario Gaetano Martino, Department ¨ of Human Pathology, Messina, Italy; 2 Universitatsklinik fur ¨ Innere Medizin ¨ V, Hamatologie & Onkologie, Innsbruck, Austria; 3 University of Messina, Department of Biolagical and Enviromental Sciences, Messina, Italy; 4 Hospital of Bolzano, Department of Hematology & CBMT, Bolzano, Italy Background: Mantle cell lymphoma (MCL) is an aggressive non-Hodgkin lymphoma (NHL) accounting for about 6% of all new diagnoses. Although its typical onset is characterized by the absence of B symptoms and good performance status of the patients, MCL is a highly aggressive lymphoma with a dismal prognosis. Up to now the most promising results have been obtained with immunochemotherapy followed by autologous cell stem transplantation (ASCT) but the number of relapses is still high and the disease remains uncurable. In the last years, Yttrium-90 (90 YIT) ibritumomab proved to be an efficient treatment for MCL, which was able to induce in at least some of the investigated patients negativity of minimal residual desease (MRD). The aim of the present analysis was to evaluate the feasibility and efficacy of 90 Y-IT consolidation after immunochemotherapy followed by ASCT. Patients and Methods: We retrospectively assessed 57 patients affected by intermediate or high-risk MCL who received in first line 3 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine and dexamethasone (R-CHOP) plus 3 cycles of rituximab, dexametasone, cytarabine, cisplatin
(R-DHAP) followed by ASCT. 28 underwent and additional consolidation treatment with 90 Y-IT. Subsequently all patients underwent 2-years of rituximab maintenance. Results: R-CHOP plus R-DHAP chemotherapy achieved a high response rate (CR 83% and PR 12%) and only one patient progressed during induction treatment. Successive treatment intensification with BEAM chemotherapy and ASCT was able to improve ORR to 98% by inducing a CR in 5 more patients (CR 95% and PR 5%). All patients who underwent subsequent 90 Y-IT achieved a CR. Seven out of the 26 patients in CR at the beginning of rituximab maintenance in the control group (27%) and 1/28 (3%) in the 90 Y-IT group experienced relapse (p = 0.01) during treatment. The median follow-up was 6.2 years. Two patients (7%) of the control group suffered disease progression and 14 (50%) a relapse compared to 7 relapses in the 90 Y-IT arm (p = 0.02). Treatment intensification significantly prolonged median PFS (not reached versus 5.3 years, p = 0.0005) and OS (not reached versus 8.1 years, p = 0.008). Unlike the control arm, MIPI score and bone marrow infiltration did not significantly influence OS and PFS in the 90 Y-IT group. Adding 90 Y-IT was safe and did not increase treatment-related toxicity. Conclusion: In conclusion, immunochemotherapy followed by ASCT resulted in very high response rate and subsequent 90 Y-IT consolidation significantly reduced the number of relapses and increased survival. These promising results suggest that 90 Y-IT consolidation is a valid option in first line treatment. However, a prospective, confirmatory trial is warranted. No conflict of interest. 3220 POSTER Response to two treatment regimens in adult Egyptian patients with Burkitt’s lymphoma T. Abdel Hamid1 , H. Mahmoud1 , F. Abu-Taleb2 , A. Ahmed2 , A. Salama3 , R. Haggag2 , H. Khaled1 . 1 National Cancer Institute Cairo, Medical Oncology/Hematology, Cairo, Egypt; 2 Zagazig University, Medical Oncology, Zagazig, Egypt; 3 National Cancer Institute Cairo, Pathology Department, Cairo, Egypt Background: Burkitt’s lymphoma (BL) is an aggressive B-cell non-Hodgkin lymphoma. It has rapid growth with a very short doubling time. Patients with BL require intensive, frequent multi-agents therapy with adequate CNS prophylaxis. Aim: Evaluate the treatment outcome of adult BL patients and their toxicity profiles using two different protocols at two different Egyptian centers. Patients and Method: This is a retrospective study included 37 adult BL patients diagnosed at the NCI − Cairo University and Medical Oncology Department Zagazig University in the period from 2006 to 2012. We used St Jude/Murphy staging system and NCCN guidelinesfor risk stratification. Pathology of all cases was revised at pathology department NCI − Cairo. Patients were categorized into group A (n = 20) Treated at NCI Cairo with modified CALGB regimen (with higher methotrexate dose of 3gm/m2 ) and group B (n = 17) treated at Zagazig University Hospital with modified hyper C VAD regimen (with reduced cytarabine dose 1gm/m2 ) Results: Median age in group A was 31 compared to 36 years in group B (p = 0.024). There was male predominance in group A, but in group B, female predominance was reported (p = 0.015). Out of 13 evaluable cases in group A, the CR rate was 76.9% compared to 70.6% for the 17 patients in group B with no significant difference. Median DFS and OS were not reached. The mean DFS for group A was 79.09±8.09 months (95% CI: 63.22 to 94.96) while for group B it was 32.02±3.41 months (95% CI: 25.33 to 38.70) (p = 0.69). The mean OS for the 20 patients of group A was 52.03±9.85 months (95% CI: 32.72 to 71.35), Compared to a mean of 31.42±3.67 months (95% CI: 24.22 to 38.61) for group B (p = 0.15). In group A, there is significant relation between OS and sex, performance status, LDH and risk but near significant relation with disease stage (p = 0.07).While in group B, there was significant relation with B symptoms and number of extranodal sites. Grade 3 and 4 hematologic toxicity was higher in group A compared to B. In group A, five patients (27.8%) showed early death before chemotherapy evaluation and three patients (12.2%) died due to disease progression. In group B, there were four deaths (23.5%) due to disease progression. Conclusions: In view of recent progress in management of BL, modification of our protocols to improve the CR rate is needed. The toxicity related early mortality with the modified CALGB protocol is high that highlights the need of adequate supportive care including growth factors and Methotrexate dose reduction in older patients. Modified hyper CVAD protocol used in this study showed higher rate of relapse, so it is recommended only for low risk cases and those with comorbidity. No conflict of interest.
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3218 POSTER PACEBOM in relapsed/refractory (R/R) lymphoma in the rituximab (R) era B. Tamjid1 , J. McKendrick2 , R. Doig2 , P. Hosking3 , P. James2 , S. Anthony2 , E. Hawkes2 . 1 Austin Hospital, Medical Oncology, Heidelberg Melbourne, Australia; 2 Eastern Health, Medical Oncology, Melbourne, Australia; 3 Eastern Health, Pathology, Melbourne, Australia Background: R/R lymphoma outcomes are poor. There is no standard treatment. PACEBOM has efficacy for several lymphoma subtypes however most published reports are the 1990’s, prior to routine R for B-cell lymphoma. We evaluate PACEBOM+/-R for R/R lymphoma in this millennium. Methods: In this retrospective, single-centre study, R/R lymphoma patients who received PACEBOM (prednisolone, doxorubicin, cyclophosphamide, etoposide, bleomycin, vincristine, methotrexate) were identified from the pharmacy database. Demographic, treatment, toxicity and survival data were collected. The study was approved by the local IRB. Results: 69 eligible pts were identified. 56/69 were male. Median age was 56.5 yrs. Histological subtypes included 20 DLBCL, 18 FL, 10 TCL, 7 HL, 14 other indolent subtypes. 46(67%) received 2nd line PACEBOM, 23(33%) had 2 prior regimens. 48/52 B-cell NHL had prior R. Median number of cycles was 6 (range 1−6). 29/69 received R-PACEBOM. Overall response rate (ORR) was 72%, 75% in pts who received prior R, and 80% in the R-PACEBOM cohort. 15 pts underwent ASCT post-PACEBOM. Median follow-up was 57 months (m) (3–201). Median PFS & OS post-PACEBOM was 12.4m (range 0−89) & 20.6m(range 0−89). In B-cell NHL pts who had prior R, PFS & OS were improved with R-PACEBOM vs PACEBOM alone (PFS 18m vs 11m, OS not reached vs 16.3m). Most common grade3−4 toxicities were neutropenia (41%), anaemia (16%) & thrombocytopaenia (13%). No difference in toxicity was seen between patients who received R vs no R. Conclusion: PACEBOM is active across all R/R lymphoma subtypes with manageable toxicity and can be safely combined with R. Outcomes were similar to reports of other salvage regimens. PACEBOM remains a suitable option for R/R lymphoma, in pts exposed to prior R & planned for ASCT. Table: ORR by subtype Subtype
ORR, n/N (%)
All DLBCL HL TCL Other indolent lymphomas
50/69 (72%) 13/20 (65) 5/7 (71) 7/10 (70) 25/32 (78)
No conflict of interest. 3219 POSTER 90Y-ibritumomab-tiuxetan consolidation for advanced stage mantle cell lymphoma after first line autologous stem cell transplantation: Is it time for a step forward? P. Mondello1 , N. Steiner2 , S. Cuzzocrea3 , W. Willenbacher2 , C. Arrigo1 , V. Pitini1 , M. Mian4 . 1 Policlinico Universitario Gaetano Martino, Department ¨ of Human Pathology, Messina, Italy; 2 Universitatsklinik fur ¨ Innere Medizin ¨ V, Hamatologie & Onkologie, Innsbruck, Austria; 3 University of Messina, Department of Biolagical and Enviromental Sciences, Messina, Italy; 4 Hospital of Bolzano, Department of Hematology & CBMT, Bolzano, Italy Background: Mantle cell lymphoma (MCL) is an aggressive non-Hodgkin lymphoma (NHL) accounting for about 6% of all new diagnoses. Although its typical onset is characterized by the absence of B symptoms and good performance status of the patients, MCL is a highly aggressive lymphoma with a dismal prognosis. Up to now the most promising results have been obtained with immunochemotherapy followed by autologous cell stem transplantation (ASCT) but the number of relapses is still high and the disease remains uncurable. In the last years, Yttrium-90 (90 YIT) ibritumomab proved to be an efficient treatment for MCL, which was able to induce in at least some of the investigated patients negativity of minimal residual desease (MRD). The aim of the present analysis was to evaluate the feasibility and efficacy of 90 Y-IT consolidation after immunochemotherapy followed by ASCT. Patients and Methods: We retrospectively assessed 57 patients affected by intermediate or high-risk MCL who received in first line 3 cycles of rituximab, cyclophosphamide, doxorubicin, vincristine and dexamethasone (R-CHOP) plus 3 cycles of rituximab, dexametasone, cytarabine, cisplatin
(R-DHAP) followed by ASCT. 28 underwent and additional consolidation treatment with 90 Y-IT. Subsequently all patients underwent 2-years of rituximab maintenance. Results: R-CHOP plus R-DHAP chemotherapy achieved a high response rate (CR 83% and PR 12%) and only one patient progressed during induction treatment. Successive treatment intensification with BEAM chemotherapy and ASCT was able to improve ORR to 98% by inducing a CR in 5 more patients (CR 95% and PR 5%). All patients who underwent subsequent 90 Y-IT achieved a CR. Seven out of the 26 patients in CR at the beginning of rituximab maintenance in the control group (27%) and 1/28 (3%) in the 90 Y-IT group experienced relapse (p = 0.01) during treatment. The median follow-up was 6.2 years. Two patients (7%) of the control group suffered disease progression and 14 (50%) a relapse compared to 7 relapses in the 90 Y-IT arm (p = 0.02). Treatment intensification significantly prolonged median PFS (not reached versus 5.3 years, p = 0.0005) and OS (not reached versus 8.1 years, p = 0.008). Unlike the control arm, MIPI score and bone marrow infiltration did not significantly influence OS and PFS in the 90 Y-IT group. Adding 90 Y-IT was safe and did not increase treatment-related toxicity. Conclusion: In conclusion, immunochemotherapy followed by ASCT resulted in very high response rate and subsequent 90 Y-IT consolidation significantly reduced the number of relapses and increased survival. These promising results suggest that 90 Y-IT consolidation is a valid option in first line treatment. However, a prospective, confirmatory trial is warranted. No conflict of interest. 3220 POSTER Response to two treatment regimens in adult Egyptian patients with Burkitt’s lymphoma T. Abdel Hamid1 , H. Mahmoud1 , F. Abu-Taleb2 , A. Ahmed2 , A. Salama3 , R. Haggag2 , H. Khaled1 . 1 National Cancer Institute Cairo, Medical Oncology/Hematology, Cairo, Egypt; 2 Zagazig University, Medical Oncology, Zagazig, Egypt; 3 National Cancer Institute Cairo, Pathology Department, Cairo, Egypt Background: Burkitt’s lymphoma (BL) is an aggressive B-cell non-Hodgkin lymphoma. It has rapid growth with a very short doubling time. Patients with BL require intensive, frequent multi-agents therapy with adequate CNS prophylaxis. Aim: Evaluate the treatment outcome of adult BL patients and their toxicity profiles using two different protocols at two different Egyptian centers. Patients and Method: This is a retrospective study included 37 adult BL patients diagnosed at the NCI − Cairo University and Medical Oncology Department Zagazig University in the period from 2006 to 2012. We used St Jude/Murphy staging system and NCCN guidelinesfor risk stratification. Pathology of all cases was revised at pathology department NCI − Cairo. Patients were categorized into group A (n = 20) Treated at NCI Cairo with modified CALGB regimen (with higher methotrexate dose of 3gm/m2 ) and group B (n = 17) treated at Zagazig University Hospital with modified hyper C VAD regimen (with reduced cytarabine dose 1gm/m2 ) Results: Median age in group A was 31 compared to 36 years in group B (p = 0.024). There was male predominance in group A, but in group B, female predominance was reported (p = 0.015). Out of 13 evaluable cases in group A, the CR rate was 76.9% compared to 70.6% for the 17 patients in group B with no significant difference. Median DFS and OS were not reached. The mean DFS for group A was 79.09±8.09 months (95% CI: 63.22 to 94.96) while for group B it was 32.02±3.41 months (95% CI: 25.33 to 38.70) (p = 0.69). The mean OS for the 20 patients of group A was 52.03±9.85 months (95% CI: 32.72 to 71.35), Compared to a mean of 31.42±3.67 months (95% CI: 24.22 to 38.61) for group B (p = 0.15). In group A, there is significant relation between OS and sex, performance status, LDH and risk but near significant relation with disease stage (p = 0.07).While in group B, there was significant relation with B symptoms and number of extranodal sites. Grade 3 and 4 hematologic toxicity was higher in group A compared to B. In group A, five patients (27.8%) showed early death before chemotherapy evaluation and three patients (12.2%) died due to disease progression. In group B, there were four deaths (23.5%) due to disease progression. Conclusions: In view of recent progress in management of BL, modification of our protocols to improve the CR rate is needed. The toxicity related early mortality with the modified CALGB protocol is high that highlights the need of adequate supportive care including growth factors and Methotrexate dose reduction in older patients. Modified hyper CVAD protocol used in this study showed higher rate of relapse, so it is recommended only for low risk cases and those with comorbidity. No conflict of interest.