scholarly journals Treatment of Feline Gastrointestinal Small-Cell Lymphoma With Chlorambucil and Glucocorticoids

2010 ◽  
Vol 46 (6) ◽  
pp. 413-417 ◽  
Author(s):  
Timothy J. Stein ◽  
MacKenzie Pellin ◽  
Howard Steinberg ◽  
Ruthanne Chun
Keyword(s):  
Response Rate ◽  
Cell Lymphoma ◽  
Small Cell ◽  
Clinical Response Rate ◽  
Minimal Amount ◽  
Second Malignancy ◽  
Full Thickness ◽  
Neoplastic Lymphocytes ◽  
Relapsed Disease

Gastrointestinal (GI) lymphoma is the most frequently diagnosed form of lymphoma in the cat and is categorized into two distinct forms based on the size of neoplastic lymphocytes. Treatments for both large- and small-cell GI lymphoma have been described previously; however, multiple chemotherapy protocols were used, a minimal amount of histopathological characterization was provided, and, in most studies, the majority of diagnoses were obtained via endoscopic pinch biopsies. Twenty-eight cats (24 with full-thickness intestinal biopsies) were diagnosed with small-cell GI lymphoma and treated with a combination of chlorambucil and glucocorticoids. The majority of cases were strongly CD3+, and many displayed epitheliotropism. The overall clinical response rate was 96%, with a median clinical remission duration of 786 days. Follow-up identified seven cats with relapsed disease—all of which were treated with a rescue protocol of cyclophosphamide and glucocorticoids; the response rate was 100%, and four of the 28 cats were diagnosed with a second malignancy.

Multimodal Dose Dense Therapy for Mantle Cell Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5501-5501
Author(s):  
Sam O. Wanko ◽  
Jon P. Gockerman ◽  
Joseph O. Moore ◽  
Carlos de Castro ◽  
Louis Diehl ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Mantle Cell Lymphoma ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Newly Diagnosed ◽  
Mantle Cell ◽  
Dose Dense ◽  
Relapsed Disease ◽  
Cmv Reactivation

Abstract BACKGROUND: With the poor prognosis and outcome described in mantle cell lymphoma (MCL), there is a continuing need to explore treatment options that might overcome suspected underlying drug resistance and improve the current median survival of about 24 months. One strategy to overcome drug resistance has been the use of high dose therapy followed by autologous transplant. Newer agents such as the monoclonal antibodies (MoAb) rituximab and alemtuzumab which target CD20 and CD52 respectively have recently become available. We have therefore incorporated both a dose dense approach in combination with these antibodies to treat newly diagnosed and relapsed MCL patients. PATIENTS AND METHODS: A total of 16 patients have been enrolled since February 2003. Induction therapy consisted of 1 cycle of cytarabine 3gm/m2 IV Q12H for 8 doses, mitoxantrone 10mg/m2 daily for 3 days, and Alemtuzumab 30mg IV 3 times a week for 6 weeks with growth factor support. All responding patients were mobilized with cyclophosphamide 4gm/m2 and G-CSF 10 mcg/kg/day and/or bone marrow harvest. The transplant preparative regimen was carmustine 15mg/kg on day -6, etoposide 60mg/kg on day -4, and cyclophosphamide 100mg/kg on day -2 followed by autologous re-infusion. Consolidation was given with rituximab 375mg/m2 weekly for 4 doses at 6 weeks and 6 months post transplant. RESULT: Of the 16 patients, 12 had stage IV, 1 stage III, 3 stage IIA, and 1 stage I disease. The median age was 60 (48 66 years). Eight were newly diagnosed and 8 had relapsed disease with at least 2 prior chemotherapy treatments. In the induction phase, overall response rate was 94% (15/16 patients) with 73% complete response (CR) and 27% partial response (PR). Response rate were 100% and 88% in the newly diagnosed and relapsed patients respectively but CR was similar (75%) in both groups. Nine patients have been transplanted and one patient is awaiting transplant. Six patients were not transplanted due to death in 2 patients with relapsed disease at study entry, and one each due to progression of disease, prolonged cytopenias of > 60days, mental status changes and inability to collect peripheral or bone marrow stem cell respectively. Among the transplanted patient, 78% (7/9) remain in CR with 2-year lymphoma progression free survival of 67% after a median follow-up of 487 days (range 175–787 days). Induction therapy toxicities included average neutropenia duration of 11.6 days and CMV reactivation of 50% that was equally distributed in the transplanted and non-transplanted patients. Peripheral stem cell collection was inadequate in 5 of the transplanted patients requiring bone marrow harvest. CONCLUSION: Our preliminary data continue to show a high induction response rate with majority of patients who are able to proceed to the transplant phase remaining free of lymphoma at 24 months. Toxicity was manageable although bone marrow harvest was needed to obtain adequate stem cells in majority of transplanted patients. While CMV reactivation was observed in half of the patients, its effect on the ability of subjects to complete the study and on survival appear to be minimal. Although a small study, multimodal dose dense strategy with maintenance MoAb for patients with mantle cell lymphoma is a promising strategy that needs to be confirmed in larger number of patients with prolonged follow-up.

Randomized trial of three combinations of cisplatin with vindesine and/or VP-16-213 in the treatment of advanced non-small-cell lung cancer.

1985 ◽  
Vol 3 (2) ◽  
pp. 176-183 ◽  
Author(s):  
H M Dhingra ◽  
M Valdivieso ◽  
D T Carr ◽  
D F Chiuten ◽  
P Farha ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Median Survival ◽  
Cell Lung Cancer ◽  
Response Rate ◽  
Small Cell ◽  
High Dose ◽  
Small Cell Lung ◽  
To Receive

One hundred sixty-seven evaluable patients with non-small-cell lung cancer were randomized to receive high-dose cisplatin and vindesine (PVD), or cisplatin and VP-16-213 (etoposide epipodophyllotoxin) (PVP), or cisplatin with VP-16-213 and vindesine (PVPVD). The patient distribution and characteristics were similar in all the treatment arms. The response rate differences (35% in PVD arm, 30% in PVP arm, and 22% in PVPVD arm) were not statistically significant (P = .33). Response durations were 43 weeks in the PVD arm, 20 weeks in the PVP arm, and 27 weeks in the PVPVD arm. Median survival was 29 weeks in the PVD and PVP arms and 28 weeks in the PVPVD arm. Median survival time of responding patients was 76 weeks in the PVD arm and 65 weeks in the PVP arm; 78% of patients were alive at 22+ to 87+ weeks follow-up in the PVPVD arm. Myelosuppression was similar in all three treatment arms. Significantly more azotemia occurred in the PVD arm than in the PVP and PVPVD arms (P = .002), and significantly more neuropathy in the PVD and PVPVD arms than in the PVP arm (P = .003 and .005). All the treatment arms have similar antitumor activity in non-small-cell lung cancer, but the PVP combination is slightly less toxic than the PVD and PVPVD treatment arms.

Multimodal Dose Dense Therapy for Mantle Cell Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1163-1163
Author(s):  
Sam O. Wanko ◽  
Jon P. Gocherman ◽  
Joseph O. Moore ◽  
Carlos Decastro ◽  
Robert Prosnitz ◽  
...  
Keyword(s):  
Mantle Cell Lymphoma ◽  
Induction Therapy ◽  
Response Rate ◽  
Cell Lymphoma ◽  
High Dose ◽  
Event Free Survival ◽  
Free Survival ◽  
Mantle Cell ◽  
Dose Dense

Abstract BACKGROUND: Mantle cell lymphoma (MCL) typically has a poor outcome with overall survival of only 3–4 years. Higher treatment response and event-free survival has been demonstrated with aggressive high dose chemotherapy followed by autologous hematopoietic stem cell support, though long term cure rates remain unclear(Dreger P. Hematol J. 2000;vol.2). Modest response rates have also been reported with the monoclonal antibody (MoAb) rituximab and ALEMTUZUMAB (Foran, JM. JCO 2000; vol. 2. Faderl S. Blood 2003; vol. 9). We therefore combined dose-dense therapy with MoAbs to explore response rate and event free survival (EFS) in mantle cell lymphoma. The strength of this trial design is ability to follow all patients from induction chemotherapy through high dose therapy and transplant in order to gauge clinical outcome on all enrolled patients, not just the subpopulation who is able to proceed to high dose therapy. PATIENTS AND METHODS: Induction therapy consisted of 1 cycle of high dose cytarabine (3gm/m2 IV over 1 hour Q12H for 8 doses), mitoxantrone (10mg/m2 daily for 3 days), and ALEMTUZUMAB 30mg IV 3 times a week for 6 weeks with growth factor support. All responding patients were mobilized with cyclophosphamide 4gm/m2 and G-CSF 10 mcg/kg/day and/or bone marrow harvest. The transplant preparative regimen was carmustine 15mg/kg over 2 hours day -6, etoposide 60mg/kg over 4 hours day -4, and cyclophosphamide 100mg/kg over 2 hours day -2 followed by autologous reinfusion on day zero. Consolidation was given with rituximab 375mg/m2 weekly for 4 doses at 6 weeks and 6 months post transplant. RESULT: 9 patients with advanced disease (7 stage IV, 1 stage III, 1 stage IIA) and median age of 60 (48 – 65 years) have been accrued and treated since February 2003. Four were newly diagnosed and 5 had relapsed/refractory disease. Seventy eight percent (7/9) had complete response and 22% (2/9) had partial response (PR) following induction therapy. One patient had severe infection after induction and was unable to proceed to transplant. Another had constitutional decline preventing further therapy and each died within 4 months of withdrawal from the protocol. Both had relapse/refractory disease at accrual. The remaining 7 patients proceeded to the transplant phase. With a median follow-up of 7 months (range 3–16 months), all 7 patients remain in CR for 1 –16 months. Significant induction therapy toxicity included neutropenia in all 9 patients with average duration of 10.7 days, non-disseminated CMV reactivation in 44% of patients, one overwhelming fungal infection, and one patient with delay in engraftment. Figure Figure CONCLUSION: Our preliminary data show a high induction and transplant phase completion rate, manageable toxicity, and excellent overall response rate in this group of elderly patients with advanced disease. Larger numbers of patients and longer follow-up is needed to confirm these promising results.

Survival Benefits of Patients with Non-Hodgkin’s Lymphoma Treated with Rituximab Combined with Chemotherapy.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4625-4625
Author(s):  
Zhixiang Shen ◽  
Junmin Li ◽  
Aihua Wang ◽  
Yu Chen
Keyword(s):  
B Cell ◽  
Overall Response Rate ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
Free Survival ◽  
Overall Response ◽  
Large B Cell

Abstract Purpose: Rituximab combined with chemotherapy has been recommended as first-line or second-line standard regimen in most subtypes of B-cell lymphoma in China by the 2004 National Comprehensive Cancer Network lymphoma therapy guideline. We have conducted a multicenter trial to evaluate the efficacy and safety of rituximab in combination with standard chemotherapy (CHOP) in patients with previously untreated or relapsed indolent and aggressive NHL. Methods: Patients received 4–8 cycles of rituximab plus CHOP every 21 days. For each cycle, rituximab (375mg/m2) was given on day 1 and CHOP started on day 3. CHOP consisted of cyclophosphamide 750mg/m2, doxorubicin 50mg/m2, and vincristine 1.4mg/m2 (maximum 2mg/dose) given intravenously on day 3, and oral prednisone 100mg on days 3–7. Results: A total of 221 patients were enrolled on the trial, 128 males and 93 females with a mean age of 49 years (range 10–83 years). The main lymphoma subtypes were small lymphocytic (15 patients, 7%), follicular (27 patients, 12%), and diffuse large B-cell (160 patients, 72%). In total, 56 patients had indolent NHL and 165 aggressive NHL. The overall response rate for all patients was 86% with 57% complete responses. In patients with indolent NHL the overall and complete response rates were 95% and 55% respectively. After a median 12 months follow up, progression-free survival in patients with indolent NHL was 88%±5% at 1 year and 83%±6% at 2 years. In the 160 patients with diffuse large B-cell lymphoma, the overall response rate was 88% with 61% complete responses, and after a mean follow-up of 6 months, predicted 1-year and 2-year progression-free survival were 88%±5% and 83%±7% respectively. Infusion-related adverse events occurred in 4% of patients, associated with the first infusion of rituximab. Subanalyses according to subtype, stage, IPI and other factors will be presented. Conclusion: Rituximab plus chemotherapy is an effective, well-tolerated treatment that achieves high response rates and long progression-free survival in both indolent and aggressive NHL.

Favorable Results of Rituximab in Combination with CHOP in the Front-Line Treatment of Follicular Lymphoma Grade 3.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2770-2770
Author(s):  
Luis Fayad ◽  
Michael Overman ◽  
Barbara Pro ◽  
Peter McLaughlin ◽  
Felipe Samaniego ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
B Cell ◽  
Response Rate ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Bulky Disease ◽  
Large B Cell Lymphoma ◽  
Grade 3 ◽  
Large B Cell

Background: Follicular lymphoma grade 3 has a natural history that is more akin to that of diffuse large B-cell lymphoma. The addition of rituximab to standard CHOP has resulted in improved response and survival in diffuse large B-cell lymphoma. Information about outcomes in follicular lymphoma grade 3 is lacking. Methods: A single institution retrospective review of patients with follicular grade 3 lymphoma evaluated at the UTMDACC from 1999 to 2004. Patients were located from the UTMDACC lymphoma database. All patients were initially treated with R-CHOP. Results: Forty-five patients were identified: 51% male, 47% ≥60 years, and 87% follicular grade 3b. The LDH was elevated in 24%, ECOG performance status was >1 in 2%, and >1 site of extranodal involvement was present in 10%. Stage distribution was 11% stage I, 11% stage II, 42% stage III, and 36% stage IV, bulky disease (>7cm) was present in 11%, and B symptoms occurred in 13%. Beta-2 microglobulin was elevated in 57% with values >3 μg/dL in over 50%. IPI distribution was: 46% IPI Low, 38% LI, 11% IH, and 4% IPI High. Overall response rate was 100% with 96% complete responses. Relapse rate by IPI category was 24% for Low IPI, 18% for IPI LI, and 40% for IPI IH, and 100% for the two patients with High IPI. With median follow-up of 33 months, three year failure-free survival (FFS) is 73% (95% CI: 59 to 87%). One patient died (2%) with an overall survival (OS) at three years of 97% (95% CI: 93 to 100%). Conclusion: The addition of rituximab to CHOP provided a high response rate and excellent early survival in this group of mostly good prognosis patients. Relapses were still seen; longer follow-up is needed.

Arsenic Trioxide with Ascorbic Acid and High-Dose Melphalan Is Safe and Effective for Autotransplantation for Multiple Myeloma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 942-942 ◽  
Author(s):  
Muzaffar H. Qazilbash ◽  
Rima M. Saliba ◽  
Gaurav Parikh ◽  
Chitra Hosing ◽  
Floralyn Mendoza ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Ascorbic Acid ◽  
Arsenic Trioxide ◽  
Response Rate ◽  
Hematopoietic Progenitor Cell ◽  
High Dose ◽  
Preparative Regimen ◽  
Relapsed Disease ◽  
High Dose Melphalan

Abstract Background: Arsenic trioxide (ATO) has been shown to be synergistic with melphalan both in vitro and in vivo. We conducted a randomized phase II trial to determine the safety and efficacy of a combination of ATO, melphalan, and ascorbic acid (AA) as a preparative regimen in patients undergoing autologous hematopoietic progenitor cell transplantation for multiple myeloma (MM). We also assessed the impact of ATO levels on melphalan pharmacokinetics, engraftment, and toxicity. Methods: Forty-eight patients with secretory myeloma (23 females, 25 males; median age, 54; range 35–70) were treated between 4/04 and 8/05. All patients received melphalan 100 mg/m2 IV on days -4 and -3 and AA 1000 mg/day IV on days -9 to -3. Patients were randomized to 3 arms: no ATO (arm 1), ATO 0.15 mg/kg IV on days -9 to -3 (arm 2), and ATO 0.25 mg/kg IV on days -9 to -3 (arm 3). Twelve patients had received a prior autograft, with a median 4.5 x 106/kg (range 2.3–10.9) CD34+ cells infused. Results: Patients in all 3 arms were evenly matched. Twenty-nine patients (60%) were transplanted for consolidation of first remission and 19 patients (40%) for relapsed disease. With a median follow-up of 26 months (range 10–37) post-autograft, no dose-limiting toxicity, or nonrelapse mortality was reported. Toxicity was limited to grade 1 or 2 nausea, vomiting, and diarrhea and was comparable in all 3 arms. Melphalan pharmacokinetics was not altered by ATO pretreatment. Median time to neutrophil engraftment (absolute neutrophil count >500/dL) was 9 days, with no engraftment failures or delays in either the control or ATO arms. The complete response (CR) rate for all patients was 25% (12/48), and the partial response rate was 60% (29/48) for an overall response rate (ORR = CR + PR) of 85%. Progression-free survival (PFS) and overall survival (OS) after 24 months of follow-up were 59% and 91%, respectively. Median PFS was 29 months; median OS has not been reached. There was no significant difference in CR, ORR, PFS, or OS among the 3 arms (P =.9, .9, .5, and .6, respectively). PFS and OS were comparable among patients with chromosomal abnormalities or relapsed disease at transplant and patients undergoing a second autotransplant for salvage. Conclusions: Addition of ATO + AA to high-dose melphalan is safe and well tolerated as a preparative regimen for autotransplants in patients with MM, including high-risk patients. There was no adverse impact of ATO on engraftment. Longer follow-up is necessary to assess the efficacy of this combination on PFS and OS.

The VcR-CVAD Regimen Produces a High Complete Response Rate in Untreated Mantle Cell Lymphoma (MCL): First Analysis of E1405 – A Phase II Study of VcR-CVAD with Maintenance Rituximab for MCL.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1661-1661 ◽  
Author(s):  
Brad S Kahl ◽  
Hailun Li ◽  
Mitchell R Smith ◽  
Randy D. Gascoyne ◽  
Elisabeth Paietta ◽  
...  
Keyword(s):  
Phase Ii ◽  
Research Funding ◽  
Response Rate ◽  
Complete Response Rate ◽  
Phase Ii Study ◽  
Cell Lymphoma ◽  
Complete Response ◽  
Mantle Cell ◽  
Grade 3

Abstract Abstract 1661 Poster Board I-687 Introduction One approach to improving outcomes in Mantle Cell Lymphoma (MCL) is to incorporate newer targeted agents into standard chemotherapy regimens. As the proteasome inhibitor bortezomib (Velcade‘) achieved a 33% response rate in relapsed MCL, we hypothesized that the incorporation of Velcade (Vc) into a modified R-hyperCVAD chemotherapy backbone would result in a high complete response rate (CR). The new regimen, VcR-CVAD, was tested for safety and efficacy in a phase II study within the Wisconsin Oncology Network (UW) and demonstrated a CR rate of 77% (Kahl, ASH 2008). To determine the safety and efficacy of this regimen in a cooperative group setting, we initiated E1405: a phase II study of VcR-CVAD with maintenance rituximab (MR) for untreated MCL. Methods Eligible patients had histologically confirmed, previously untreated MCL, PS 0-2, and adequate end organ function. The treatment plan included: Velcade 1.3 mg/m2 days 1 and 4, rituximab 375 mg/m2 IV day 1, cyclophosphamide 300 mg/m2 IV over 3 hrs q 12 hrs X 6 doses days 1-3, doxorubicin 50 mg/m2 continuous infusion over 48 hrs days 1-2, vincristine 1 mg IV day 3, dexamethasone 40 mg po days 1-4. Cycles were repeated every 21 days for 6 cycles and all patients received G-CSF support. Patients achieving SD, PR, or CR received MR administered as 4 weekly treatments every 6 months for 2 years (protocol therapy). Patients had an option to receive high dose chemotherapy and autologous stem cell transplantation (off protocol) rather than MR. The primary endpoint of the trial was the CR rate, incorporating PET imaging, to VcR-CVAD induction therapy. Results Seventy-six eligible patients were enrolled between 5/07 and 10/08. Baseline characteristics include median age 62 (40-76), 59M:17F, 91% stage III/IV, and 39% with elevated LDH. Sixty-four patients (84%) completed VcR-CVAD induction therapy. Reasons for treatment discontinuation included PD (1), toxicity (4), patient preference (2), and other/unknown (5). Response information is available on 74 patients while data is outstanding on 2 patients. The ORR was 96% (73/76; 95% CI, 89%-99%), CR rate 75% (57/76; 95% CI, 64%-84%) and the PR rate 21% (16/76; 95% CI, 13%-32%). Six of the PR patients were coded as such because of protocol violations in which a post-treatment bone marrow biopsy or PET scan was not obtained. The CR rate in the 68 completely restaged patients was 84%. Forty-four patients proceeded to planned MR while 21 patients went off protocol to SCT consolidation. Median follow up is currently too short (9 months) to assess PFS and OS. The major toxicity of the treatment regimen was expected myelosuppression. Grade 3-4 non hematologic toxicities were rare. No patients developed grade 3-4 neuropathy. There were no treatment related deaths. Conclusion The VcR-CVAD induction produced high overall response (96%) and CR rate (75%) in a representative MCL patient population treated on a cooperative group protocol. The CR rate was high and comparable to the UW pilot study (77%). No episodes of severe painful peripheral neuropathy were reported using the reduced vincristine dosage and the overall toxicity profile was very acceptable. Longer follow up is needed to determine if the high CR rate will translate into improved PFS and OS. Disclosures Kahl: Genentech: Consultancy, Research Funding; Millennium: Consultancy, Research Funding. Off Label Use: Bortezomib as front line treatment in MCL. Smith:Genentech: Research Funding; Millennium: Research Funding. Advani:Seattle Genetics, Inc.: Research Funding. Horning:Genentech: Honoraria, Research Funding.

Phase I/II Trial of Ofatumumab/Lenalidamide for Patients with Relasped/Refractory B-Cell Non-Hodgkin Lymphoma: High Response Rate in Indolent Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3692-3692
Author(s):  
Julie M Vose ◽  
Fausto R. Loberiza ◽  
R. Gregory Bociek ◽  
Philip Bierman ◽  
James O. Armitage
Keyword(s):  
Phase I ◽  
B Cell ◽  
Hodgkin Lymphoma ◽  
Research Funding ◽  
Response Rate ◽  
Cell Lymphoma ◽  
High Response Rate ◽  
Indolent Lymphoma ◽  
Non Hodgkin Lymphoma

Abstract Abstract 3692 Introduction: Lenalidomide and ofatumumab have demonstrated clinical activity as single agents in a variety of types of non-Hodgkin lymphoma (NHL). This trial is a phase I/II trial combining these two agents for treatment of patients with relapsed and refractory B-cell NHL. Methods: Patients with relapsed and refractory B-cell NHL of any histology were enrolled on a phase I/II trial combining lenalidomide and ofatumumab. Nine patients were on the phase I part of the trial and received a fixed dose of ofatumumab 1000 mg weekly × 8 doses along with lenalidomide 15 mg (N=3), or10 mg (N=6) for 21/28 days until the time of progression. The phase II portion of the study has 28 patients on the study with adequate follow-up at the time of analysis. The phase II doses were ofatumumab 1000 mg weekly × 8 along with lenalidomide 10 mg on 21/28 days. The lenalidomide was dose adjusted according to standard dose reduction criteria. All patients were on either a daily aspirin or other anticoagulation for thrombosis (DVT) prophylaxis. Results: Thirty seven evaluable patients had adequate follow-up at the time of the analysis. The patients had a median age of 65 years (range 36–81), 76% were male, and 89% have an ECOG performance status of 0–1. The majority of patients had a relapsed indolent lymphoma with 12/37 (32%) follicular lymphoma (FL), 6/37 (16%) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), 7/37 (19%) mantle cell lymphoma (MCL), one unclassifiable indolent lymphoma (3%), and 11/37 (30%) diffuse large B-cell lymphoma (DLBLC). The median duration of follow-up of surviving patients was 13 months (range 4–24). The complete response (CR) rate was 2/37 (5%) (one each FL and DLBCL) and the partial response (PR) rate was 13/37 (35%) for an overall response rate (ORR) of 15/37 (40%). The 1 year progression-free survival (PFS) was 41% (95% CI; 23–58) and the 1-year overall survival (OS) was 68% (95% CI; 49–82). In an analysis of response by patient variables, those significant included the patients with an FL histology (ORR 83%) vs. DLBCL (ORR 18%) or other(SLL, MCL, unclassifiable) (ORR 21%) (p= 0.001) and lactic dehydrogenase (LDH) normal (ORR 56%) vs. elevated (ORR 14%) (p= 0.01). In an analysis of variables for PFS, the variables with significance include diagnosis of FL (1-year PFS 67%) vs. DLBCL (9%) and SLL, MCL, unclassifiable (45%) (p=0.002), LDH normal (1-year PFS 55%) vs. elevated LDH (1-year PFS 19%), and number of prior chemotherapies 1–2 (1-year PFS 58%) vs. > 3 (1-year PFS 19%). Higher grade toxicities included grade 4 neutropenia in 9/37 (24%), one each of grade 4 bacteremia, one grade 4 DVT, stroke, and acute renal failure. Conclusions: The combination of lenalidomide and ofatumumab was well tolerated by most patients. The patients with indolent NHL had a high response rate of 83% and a 1-year PFS of 67%. Disclosures: Vose: Glaxo Smith Kline: Research Funding; Celgene: Research Funding. Off Label Use: Lenalidamide and Ofatumumab will be discussed for use in indolent and aggressive non-Hodgkin lymphoma.

Intensified Rituximab Induction Followed By Rituximab Maintenance For Low Grade B Cell Lymphoma: A Multicenter, Phase II Study

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1797-1797
Author(s):  
Kyouhei Yamada ◽  
Morio Sawamura ◽  
Takeshi Shimomura ◽  
Makoto Takeuchi ◽  
Shuichi Hanada ◽  
...  
Keyword(s):  
Maintenance Therapy ◽  
B Cell ◽  
Phase Ii ◽  
Response Rate ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Low Grade ◽  
Rituximab Maintenance ◽  
Multicenter Phase

Abstract Introduction Rituximab has markedly improved the clinical outcomes of mature B cell lymphoma, and rituximab maintenance therapy has been shown to be beneficial, especially in low grade B cell lymphoma (LGBCL). Several studies evaluated intensified rituximab administration combined with chemotherapy. But so far, there has not been any trial of rituximab mono-therapy with intensive rituximab induction followed by maintenance. A multicenter, phase II trial was conducted to evaluate the efficacy and safety of rituximab as induction, weekly 8 doses, and maintenance therapy for 2 years for LGBCL. Patients and Methods Patients with measurable LGBCL according to the World Health Organization (WHO) classification (2001) without prior rituximab treatment and staged as II, II, or IV by Ann-Arbor, were eligible. Patients received rituximab (375 mg/m2) weekly for 8 weeks as induction therapy, and then patients who did not have progressive disease at the end of induction received maintenance therapy with 4 weeks of rituximab at six-month intervals (up to 2 years or disease progression). Duration of treatment was 2.5 years in total. The primary endpoint was the best overall response rate (ORR). The secondary endpoints were complete response rate (CRR), 3-year progression free survival (PFS), 3-year overall survival (OS), and safety. Survivals were assessed using the Kaplan-Meier method. Results Forty-one patients with a median age of 64 years (41 to 79) were enrolled at 12 institutes belonging to the Clinical Hematology Group of National Hospital Organization (CHG-NHO) of Japan from December 2005 to May 2009. The majority of disease histology was follicular lymphoma in 33 patients. Of 41 patients, 15 were diagnosed as high tumor burden based on GELF criteria, and FLIP risk grouping classified all into 12 low risk, 21 intermediate risk, and 12 high risk cases. Four relapsed cases were included, and they have all received prior systemic chemotherapy without rituximab. Of the 41 patients, 31 (75.6%) completed the planned 2.5 years therapy. The best ORR was 75.6% (31/41, 90% CI: 62.2-86.1%), with 63.4% CR. Three-year PFS at a median follow-up time of 43.0 months (5.3-72) was 79.7% (90% CI, 66.6-88.1%). Three-year OS at a median follow-up time of 49.4 months (5.3-72) was 97.4% (90% CI, 87.1-99.5%). Grade 3 toxicities were neutropenia in 2.5% (1/41), elevated ALT in 2.5% (1/41), and infection in 2.5% (1/41). There was no grade 4 toxicity. Conclusions Intensified rituximab induction and maintenance therapy was demonstrated to have high activity, with durable PFS and minimum toxicity in LGBCL patients. Although a further large-scale trial is needed, intensified rituximab induction followed by rituximab maintenance could be a good treatment in rituximab naïve LGBCL. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Efficacy and Safety Analysis of Ibrutinib-Containing Therapy for Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL): Results from a Real-World Study in China

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 1-1
Author(s):  
Qingqing Cai ◽  
Huiqiang Huang ◽  
Yuchen Zhang ◽  
Panpan Liu ◽  
Hongmei Jing ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Real World ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Therapy Group ◽  
Subdural Hemorrhage ◽  
Efficacy And Safety ◽  
Mantle Cell ◽  
Baseline Characteristics

Background: Ibrutinib, a first-in-class Bruton's tyrosine kinase (BTK) inhibitor, has been approved for the treatment of relapsed/refractory (R/R) Mantle cell lymphoma (MCL). Both single-agent ibrutinib and combination of ibrutinib with rituximab have achieved great efficacy with manageable toxicity (Wang,NEJM2013; Wang,Lancet Oncol2015; Dreyling,Lancet2015). This study, for the first time, analyzed the real-world effectiveness and tolerability of ibrutinib for MCL patients in China. Methods: This multi-center, retrospective cohort study enrolled adult patients (pts) with pathologically confirmed MCL who initiated ibrutinib-containing treatment between November 2017 (date of commercialization) and April 2020. Eligible patients were retrospectively divided into 3 subgroups to receive ibrutinib-containing treatments for different purposes: R/R MCL group, newly diagnosed MCL group and maintenance therapy group. This analysis reports the baseline characteristics, efficacy and safety profiles in R/R MCL patients. Results: A total of 67 R/R MCL pts receiving ibrutinib-containing treatment from 9 medical centers in China were included in this analysis. At ibrutinib initiation, the median age was 61.0 (range 39-81) years, 68.7% were male and 81.8% had Eastern Cooperative Oncology Group (ECOG) performance status of 0-1. Approximately three-quarters of pts (72.3%) had 1 previous line of therapy before ibrutinib. Baseline characteristics are summarized in Table 1. Of all patients enrolled, 53.7% (36/67) of pts received ibrutinib monotherapy and 46.3% (31/67) received ibrutinib-containing combination therapy. IR (ibrutinib and rituximab) (16/31, 51.6%) and IR2 (ibrutinib, rituximab and lenalidomide) (5/31, 16.1%) were the two most common combination regimens. Nine patients (29.0%) received ibrutinib plus R-chemotherapy. Although no statistically significant difference was found in listed baseline characteristics between these two groups, a larger percentage of pts with bone marrow involvement (58.1% vs 35.7%) and bulky mass (largest diameter) ≥5 cm (46.4% vs 27.3%) were observed in combination therapy group. Best overall response rate (ORR) was 65.7% (20.9% complete remission [CR]). Median time to response (TTR) was 4.1 months and median duration of response (DOR) was 18.4 months. With a median follow-up of 10.2 months, median progression-free survival (PFS) was 21.3 months (95% confidence interval [CI], 15.2 - not available [NA]) (Figure 1A). PFS rates were 86.0%, 69.8% and 47.6% at 6 months, 1 year and 2 years. With a median follow-up of 11.2 months, median overall survival (OS) was not reached with OS rates of 98.5%, 87.9% and 76.3% at 6 months, 1 year and 2 years (Figure 1B). Compared with ibrutinib monotherapy, combination therapy showed higher ORR (50.0% vs 83.9%), CR rate (8.3% vs 35.5%) and shorter TTR (median TTR, 6.0 vs 2.2 months; Logrank,p=0.0012) (Figure 2A). Although the combination therapy had a trend for better PFS, no statistically significant benefit in PFS or OS was observed (Figure 2B, C). Safety analysis focused on 55 R/R MCL pts from 3 centers with adequate adverse events information. The most common treatment emergent adverse events (TEAEs) of interest were infection (8/55, 14.6%), rash (8/55, 14.6%), bleeding (5/55, 9.1%; 1/5 was major bleeding [subdural hemorrhage]) and atrial fibrillation (3/55, 5.5%). Four pts (7.3%) experienced grade 3-4 TEAE (neutropenia, n=2; neutropenia and lung infection, n=1; subdural hemorrhage, n=1). Six pts (10.9%) had ≥1 temporary ibrutinib discontinuation due to TEAE (infection, n=3; neutropenia, n=1; rash, n=1; vomiting, n=1). One patient discontinued ibrutinib permanently due to TEAE (subdural hemorrhage). Combination therapy group showed a higher incidence of hematological TEAE (60.9% vs 39.1%) and infection (20.7% vs 7.7%). No TEAE-related death or new safety signals was recorded. Conclusion: This real-world analysis demonstrates that ibrutinib is effective and tolerable for R/R MCL in China. Ibrutinib-containing combination therapy outperformed ibrutinib monotherapy in response rate and TTR, but showed no survival benefits. The response rate data of ibrutinib monotherapy obtained from our study was different to existing clinical trial data, which may be mainly due to the short follow-up time of our study. Further analysis with longer follow-up is needed to validate these findings. Disclosures No relevant conflicts of interest to declare.

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