Rituximab + ESHAP as Salvage Chemotherapy for Relapsed/Refractory Aggressive Non-Hodgkins Lymphoma: A Phase II Trial.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 5230-5230 ◽  
Author(s):  
Lisa Hicks ◽  
R. Buckstein ◽  
E. Piliotis ◽  
J. Mangel ◽  
K. Imrie ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Response Rate ◽  
Bone Marrow Involvement ◽  
B Cell Lymphoma ◽  
Salvage Chemotherapy ◽  
Aggressive Lymphoma ◽  
Indolent Lymphoma ◽  
Preliminary Results ◽  
Cell Harvest

Abstract Background: Patients with relapsed or refractory aggressive B-cell lymphoma have a poor prognosis. If sensitive to salvage chemotherapy, high dose therapy followed by autologous stem cell transplant (ASCT) can result in long-term survival for some. Unfortunately, 50% of patients are insensitive to standard salvage regimens and thus are ineligible for ASCT. Hypothesis: Combining Rituximab with ESHAP may improve chemosensitivity and ASCT eligibility, of patients with CD20+, relapsed or refractory aggressive lymphoma, or CD20+ transformed indolent lymphoma. Objectives: The primary outcome was response rate (CR + CRu + PR) to R-ESHAP. Secondary outcomes were toxicity, ability to undergo ASCT, presence of minimal resdidual disease in the stem cell harvest, and progression free and overall survival. Methods: Eligible patients were 16–65 years old, had ECOG performance status 0–2, and had pathologically confirmed CD20+, relapsed/refractory aggressive lymphoma or transformed indolent lymphoma. Patients with refractory disease had a PR with initial anthracycline-based therapy. ESHAP (etoposide 40mg/m2 day 1–4, solumderol 500mg day 1–5, cytosine arabinoside 2g/m2 day 5, cisplatin 25mg/m2 day 1–4) was given every 28 days with GCSF support until < 15% bone marrow involvement was achieved (2–4 cycles). Eight infusions of Rituximab (375mg/m2) were administered weekly concurrent with the first 2 cycles of ESHAP. GCSF mobilized stems cells were collected on day 10 or 11 when < 15% bone marrow involvement was achieved (mainly in cycles 1 or 2). Results: Preliminary results of 14 of 44 planned patients are presented. Median age was 54 years (range 42–64). All pts had CD20+ aggressive lymphoma, 6 had relapsed aggressive lymphoma, 2 had refractory aggressive lymphoma (with PR after initial therapy) and 6 had transformed indolent lymphoma. Twelve of 14 patients were stage III/IV. The response rate to R-ESHAP was 93% (2 CR, 2 CRu, 9 PR, 1 PD). Thirteen of 14 patients proceeded to ASCT. Data on minimal residual disease in the stem cell harvest is pending. Grade 3–4 thrombocytopenia, neutropenia and anemia occurred with 53%, 31%, and 20% of R-ESHAP cycles respectively. Two of 14 patients had febrile neutropenia, one with bacteremia. Two patients had non-neutropenic bacteremia (1 with septic shock). There were no toxic deaths. Median follow-up post-ASCT is 5 months (range 1–18). Two patients progressed 4 and 5 months post-ASCT respectively. There were 3 deaths, 2 lymphoma related and 1 due to accelerated Parkinson’s Disease. Median PFS has not yet been reached. Conclusions: This trial is still accruing patients. However, preliminary results are promising. R-ESHAP appears to be well tolerated with a high response rate. This regimen may enable more patients with relapsed/refractory aggressive lymphoma or transformed indolent lymphoma to proceed to ASCT.

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

Blood ◽  
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.

Ixazomib, Dexamethasone and Rituximab in Previously Untreated Patients with Waldenström Macroglobulinemia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2956-2956 ◽  
Author(s):  
Jorge J. Castillo ◽  
Joshua Gustine ◽  
Kirsten Meid ◽  
Toni Dubeau ◽  
Guang Yang ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Median Time ◽  
Research Funding ◽  
Response Rate ◽  
Bone Marrow Involvement ◽  
B Cell Lymphoma ◽  
Induction Phase ◽  
Primary Therapy ◽  
Wild Type ◽  
Median Serum

Abstract Introduction: Waldenström's macroglobulinemia (WM) is an incurable B-cell lymphoma characterized by the accumulation of IgM-secreting lymphoplasmacytic cells in the bone marrow and other organs. Bortezomib in combination with rituximab and dexamethasone (BDR) is highly active as primary therapy in WM, though treatment-related neuropathy is common with BDR in WM, and often leads to premature treatment discontinuation. Ixazomib is an orally administered proteasome inhibitor with limited neuropathy that is active in myeloma, but has not been previously evaluated in WM Methods: Symptomatic, previously untreated patients with a clinicopathological diagnosis of WM were included in this prospective, single-arm phase II study evaluating ixazomib 4 mg PO on days 1, 8 and 15 + dexamethasone 20 mg PO/IV on days 1, 8 and 15 + rituximab 375 mg/m2 IV on day 1 (IDR) were administered for six 4-week cycles (induction) followed by six 8-week cycles (maintenance). Rituximab was held for the first two cycles of therapy to minimize risk of IgM flare. Zoster prophylaxis and proton pump inhibitors were administered throughout IDR therapy. The study was approved by the institutional review board at the Dana-Farber Cancer Institute, and registered under Clinicaltrials.gov ID NCT02400437. Results: Twenty-six WM patients were enrolled and were exposed to IDR therapy. The median age at WM diagnosis was 63 years (range 46-81 years) and the median age at initiation of therapy was 65 years (range 46-82 years). Baseline median hemoglobin was 10.2 g/dl (range 6.9-13.2 g/dL), median serum IgM level was 5,068 mg/dl (range 653-7,650 mg/dL), 46% of patients had lymphadenopathy and 12% had splenomegaly. The median bone marrow involvement was 55% (range 5-95%). The MYD88 L265P gene mutation was identified in all cases. CXCR4 gene mutations were identified in 15 patients (58%), of whom 10 (67%) had nonsense, and 5 (33%) frameshift mutations. Sixteen patients have completed the induction phase of therapy at this time. Following induction therapy, the median serum IgM level decreased to 2,316 mg/dl (range 287-5,820 mg/dL), median hemoglobin increased to 13.1 mg/dl (range 10.4-14.6 g/dL), and median bone marrow involvement decreased to 23% (range 0-76%). P-value <0.001 for all comparisons against baseline. Using consensus response criteria, the overall response rate was 88% (VGPR 6%, PR 44%, MR 38%) with a major response rate of 50%. Major responses (VGPR + PR) were observed in 47% of patients with CXCR4 mutations versus 64% in those who were wild-type CXCR4 (p=0.32). The median time to response was 8 weeks. The median time to response in CXCR4 mutant patients was 12 weeks versus 8 weeks in wild-type CXCR4 patients (log-rank p=0.03). Four patients have been taken off study; 2 for lack of response, 1 due to lack of clinical benefit with persistent failure to thrive while in PR, and 1 for progressive neuropathy while in PR although in part due to worsening of diabetic neuropathy. No other grade 3 or 4 adverse events were reported. Conclusion: These preliminary data suggest that the combination of IDR is an active and well-tolerated, neuropathy-sparing regimen in symptomatic untreated WM patients. Disclosures Castillo: Biogen: Consultancy; Otsuka: Consultancy; Abbvie: Research Funding; Pharmacyclics: Honoraria; Millennium: Research Funding; Janssen: Honoraria.

scholarly journals Impact of bone marrow involvement on outcome in relapsed and refractory transplant eligible diffuse large B-cell lymphoma and transformed indolent lymphoma

PLoS ONE ◽  
2020 ◽  
Vol 15 (7) ◽  
pp. e0235786
Author(s):  
Denis Terziev ◽  
Marcus Bauer ◽  
Lisa Paschold ◽  
Claudia Wickenhauser ◽  
Andreas Wienke ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cell ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
B Cell Lymphoma ◽  
Indolent Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

R-ICE Versus R-DHAP in Relapsed Patients with CD20 Diffuse Large B-Cell Lymphoma (DLBCL) Followed by Stem Cell Transplantation and Maintenance Treatment with Rituximab or Not: First Interim Analysis on 200 Patients. CORAL Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 517-517 ◽  
Author(s):  
Christian Gisselbrecht ◽  
Norbert Schmitz ◽  
Nicolas Mounier ◽  
David Ma ◽  
Marek Trneny ◽  
...  
Keyword(s):  
Stem Cell ◽  
Interim Analysis ◽  
Response Rate ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Salvage Chemotherapy ◽  
Early Relapse ◽  
Large B Cell Lymphoma ◽  
Intent To Treat ◽  
Large B Cell

Abstract Salvage chemotherapy followed by high dose therapy (HDT) and autologous stem cell transplantation (ASCT) is the standard of treatment for chemosensitive relapses in diffuse large B cell lymphoma. Improvement of salvage chemotherapy was suggested with the association rituximab, Ifosfamide, etoposide, carboplatinum, R-ICE. What is the optimal chemotherapy regimen and can we reduce the post ASCT relapses rate? The ongoing CORAL trial was designed to answer these questions. DLBCL CD 20+ in first relapse or pts refractory after first line therapy were randomized between rituximab plus DHAP and R-ICE. Stratification was made on centers, prior rituximab exposure and refractory/<12months relapses. Responding patients received HDT (BEAM) and ASCT and were randomized between observation and maintenance with rituximab one injection every 2 months for 1 yr. Over 400 pts have been randomized in 11 countries since 2003. The planned interim analysis was performed on the 200 first pts with a minimum follow up of 1 yr. Six pts did not receive any treatment. Intent to treat analysis was made on 194 pts (100 R ICE arm, 94 R DHAP arm): median age 55 yrs.; 86 relapses >12months, 108 refractory/early relapses; 97 pts with prior exposure to rituximab; Stage 3-4 107 pts; elevated LDH 88 pts; secondary IPI 0–1 112 pts; sIPI 2-3 63pts. The two arms were well balanced. In the prior rituximab cohort exposure more pts had refractory disease and adverse prognostic factors. However, at inclusion patients characteristics were not significantly different in the stratified subgroups. The overall response rate was 68%, with 41% complete remission rate. Toxicity was similar to what is expected with intensive therapy, 72 SAE were reported with 12 deaths during the initial salvage regimens. In univariate analysis factors significantly affecting response rate (p<.0001) were: refractory/relapse < 12 months 52% vs 88%, secondary IPI >1 54% vs 77% and prior exposure to rituximab 54% vs 82%. In a logistic regression model only refractory/early relapse and secondary IPI remain significant for response rate. Intent to treat 2 yrs EFS and OS were 50% (CI 42–57%) and 69% (CI 61–75%) respectively. Only 107 pts in this prospective study received, per protocol ASCT. For patients transplanted, 2 yrs EFS was 75% (CI 63–84%) with OS 89%. Two yrs EFS was affected by: prior treatment with rituximab, 34% vs 66% (p=.0001); refractory/early relapse 36% vs 68% (p <.0001); secondary IPI 2–3: 39% vs 0–1: 56% (p=.03). After ASCT 104 pts were randomized between observation and rituximab. Only 17% events occurred so far without unexpected toxicity, preventing to give results between the different arms according to Data Safety Monitoring Board. Conclusion: Salvage chemotherapy incorporating rituximab provide a high 82% response rate in pts not previously treated with rituximab. Patients who refractory to upfront rituximab-based chemotherapy have a poor response rate and prognosis. The study is on going to include 240 pts in the second randomisation for the EFS primary endpoint.

scholarly journals The Prognostic Value of Molecular Bone Marrow Involvement in Aggressive Lymphoma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1450-1450
Author(s):  
Neta Goldschmidt ◽  
Fares Darawshy ◽  
Elena Slyusarevsky ◽  
Galina Pogrebijski ◽  
Dina Ben Yehuda ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Conflicts Of Interest ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
B Cell Lymphoma ◽  
Aggressive Lymphoma ◽  
Prognostic Role ◽  
Negative Effect

Abstract Introduction: Morphological bone marrow (BM) involvement in diffuse Large B-cell lymphoma (DLBCL) and primary T-cell lymphoma (PTCL) has prognostic and therapeutic implications. The prognostic role of molecular BM involvement (B and T cell gene rearrangement (GR) studies), in patients with no evidence for involvement is uncertain. Objective: To evaluate the prognostic role of molecular BM involvement in patients with DLBCL and PTCL, and its significance in the rituximab era. Methods: This is a retrospective study of 416 patients with DLBCL (358) or PTCL (58) treated 1995-2010. All patients underwent BM biopsy for morphology and GR studies on BM aspirates at diagnosis and/or at end of treatment (EOT). Most patients were treated with CHOP or R-CHOP based protocols after diagnosis. Medical records were reviewed for details of initial disease characteristics, type and response to treatment, relapse if occurred and the date of death or last follow-up. Patients were classified into one of three groups according to BM results: morphology positive (MorphPos); morphology negative/GR positive (MorphNeg/GRpos); morphology negative/GR negative (MorphNeg/GRneg). Main outcome measures: Overall survival (OS) and progression free survival (PFS) among the groups of patients at diagnosis and at EOT. Results: At diagnosis there were 89 MorphPos, 49 MorphNeg/GRpos and 278 MorphNeg/GRneg patients. GRpos patients had lower complete remission rate (73.9%) than GRneg patients (84.8%; p=0.087). The median OS differed significantly among groups: MorphPos patients 66.4 months (95%CI: 50.7-82); MorphNeg/GRpos patients 89 months (95%CI: 66-111); and MorphNeg/GRneg patients 125 months (95%CI: 113-136), p<0.001. MorphNeg status improved PFS (p<0.001), however GRneg status did not (p=0.09). The hazard ratio for GRpos at diagnosis in MorphNeg patients was 1.52 (95% CI: 0.97-2.4; p=0.068). Among the subgroup of DLBCL patients, the median OS was significantly different: MorphPos patients 75.6 months (95%CI: 57.7-94.1); MorphNeg/GRpos patients 95.5 months (95%CI: 66.9-124.1); and MorphNeg/GRneg patients 129.6 months (95%CI: 118.2-141.1), p=0.036. 73% of DLBCL patients received rituximab. Rituximab improved OS (p<0.001) in all DLBCL patients, yet did not overcome the GR-positivity negative effect on OS. For PTCL patients, BM morphology and/or GR status did not affect survival. 72 patients were tested at the EOT, 5 were MorphPos and 17 GRpos. EOT MorphPos patients had marginally worse OS (p=0.07). EOT GR status in MorphNeg patients did not affect survival (p=0.5) Conclusions: BM GR positivity at diagnosis, independent of BM morphological involvement, predicts worse OS in DLBCL even in the rituximab era, but not in PTCL. EOT morphologic but not molecular involvement, had marginally negative effect on survival. Disclosures No relevant conflicts of interest to declare.

In Vivo Purge with Rituximab before Harvest Does Not Alter the Graft nor the Hematologic Recovery after Transplant.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 910-910
Author(s):  
Anne-Sophie Michallet ◽  
Sophie Tartas ◽  
Fadhela Bouaffia ◽  
Catherine Thieblemont ◽  
Olivier Hequet ◽  
...  
Keyword(s):  
Stem Cell ◽  
Median Time ◽  
Bone Marrow Involvement ◽  
Previous Treatment ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Cd34 Cells ◽  
Cell Harvest

Abstract Currently the combination of rituximab with chemotherapy is the standard for treating patients with B-cell lymphoma, particularly when high-dose therapy (HDT) plus autotranplant is scheduled, because of the in vivo purge effect of this treatment. However, the effect of rituximab on the harvest of CD34+ cells, on the hematologic recovery after transplant, and on the risk of complication was never really assessed in large series of patients. We retrospectively analyzed our data on 198 patients who were scheduled for HDT after rituximab therapy because of high failure risk, partial response, or relapse and we compared these data to a series of 207 patients treated in our center with transplant but without rituximab before stem cell harvest (Ketterer Blood1998;91:3148, BM Transplant1999;23:1309, Br J Haematol1998;103:235). Stem cells were usually harvested after chemotherapy but in case of failure were harvested at baseline. This was the case in 25 patients (15%). 29 (15%) patients failed to mobilize; all but 1 in first or second relapse and 2 patients were harvested but were not transplanted. 167 patients have been transplanted: 73 FL, 32 DLCL, 26 MCL, 15 MZL, 11 SLL, 9 MALT, and 1 BL. 44 (26%) had HDT during first line therapy. Patients who failed to mobilize had a higher number of treatment before harvest (median 3 compared to 1) and a higher frequency of bone marrow involvement at time of harvest (93% compared to 44%). The 15% failure rate is not high for these patients and was expected, suggesting that rituximab exposure was not associated with poor mobilization. Harvested patients were divided into 3 groups according to the number of CD34+ cells: low (LH) <2.5 106/kg, intermediate (IH) ≥2.5 but <10, and high (HH) ≥10 as previously described. The percentage in each subgroup was not different between patients receiving rituximab and those who did not: LH 7% and 13%, IH 77% and 62%, HH 16% and 25% for patients with and without rituximab exposure, respectively. A poorer harvest was significantly associated with fludarabine exposure (p<.0001), absence of prior rituximab exposure (p=.013), and increased number of previous treatment (p=.022). This was already the case in our previous study, except for prior rituximab exposure that seemed a favorable factor: it was observed in 48% of HH, 33% of IH, and 0% of LH. Hematologic recovery after transplant was not different from what was observed before the rituximab area and expected. Median time to ANC >1000/μl was 12 days and significantly longer in LH (12 vs. 13 days, p=.009). Median time to platelet >50 000/μl was 13 d for HH, 15 d for IH, and 22 d for LH (p=.033). Patients with LH have significantly more days with antibiotics, more platelet transfusions, and longer hospital stays but this was not different from our previous observation. 4 patients died before d100 (2.4%), all from infection. 5 other patients died before d300, all after lymphoma progression. No unexpected infection or other unexpected toxicity was observed. Rituximab as part of HDT increased the quality of response and if used for in vivo purging before stem cell harvest was not associated with a decrease quality of the harvest or with an increase of cytopenia or adverse events after transplant.

scholarly journals Relapses after Achieving EFS24 in Patients with Diffuse Large B-Cell Lymphoma in the Rituximab Era

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 454-454 ◽  
Author(s):  
Yucai Wang ◽  
Umar Farooq ◽  
Brian K. Link ◽  
Mehrdad Hefazi ◽  
Cristine Allmer ◽  
...  
Keyword(s):  
B Cell ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Salvage Chemotherapy ◽  
Newly Diagnosed ◽  
Indolent Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Introduction: The addition of Rituximab to chemotherapy has significantly improved the outcome of patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). Patients treated with immunochemotherapy for DLBCL who achieve EFS24 (event-free for 2 years after diagnosis) have an overall survival equivalent to that of the age- and sex-matched general population. Relapses after achieving EFS24 have been considered to be unusual but have been understudied. We sought to define the rate, clinical characteristics, treatment pattern, and outcomes of such relapses. Methods: 1448 patients with newly diagnosed DLBCL from March 2002 to June 2015 were included. Patients were enrolled in the Molecular Epidemiology Resource (MER) of the University of Iowa/Mayo Clinic Lymphoma SPORE, treated per physician choice (predominantly R-CHOP immunochemotherapy) and followed prospectively. An event was defined as progression or relapse, unplanned re-treatment after initial therapy, or death from any cause. Cumulative incidence of relapse and non-relapse mortality after achieving EFS24 were analyzed as competing events using Gray's test in the EZR software. Post-relapse survival was defined as time from relapse to death from any cause and analyzed using Kaplan-Meier method in SPSS (V22). Results: Among the 1448 patients, 1260 (87%) had DLBCL alone at diagnosis, and 188 (13%) had concurrent indolent lymphoma (follicular lymphoma 115, marginal zone lymphoma 18, chronic lymphocytic leukemia 14, lymphoplasmacytic lymphoma 4, unspecified 37) at diagnosis. After a median follow-up of 83.9 months, 896 patients achieved EFS24. For all 896 patients who achieved EFS24, the cumulative incidence of relapse (CIR) was 5.7%, 9.3% and 13.2%, respectively, at 2, 5 and 10 years after achieving EFS24. Patients with concurrent indolent lymphoma at diagnosis had a higher CIR compared to those with DLBCL alone at diagnosis (10.2 vs 4.8% at 2 years, 15.7 vs 8.0% at 5 years, 28.8 vs 9.7% at 10 years, P<0.001; Figure 1). There were a total of 84 patients who relapsed after achieving EFS24. The median age at initial diagnosis was 66 years (range 35-92), and 48 (57%) were male. At diagnosis, 11 (13%) had ECOG PS >1, 37 (50%) had LDH elevation, 62 (74%) were stage III-IV, 14 (17%) had more than 1 extranodal site, and 26 (31%) were poor risk by R-IPI score. There were 58 patients with DLBCL alone at diagnosis who relapsed after achieving EFS24, and 38 (75%) relapsed with DLBCL, 13 (25%) relapsed with indolent lymphoma (predominantly follicular lymphoma), and pathology was unknown in 7 patients. In contrast, there were 26 patients with concurrent indolent lymphoma at diagnosis who relapsed after achieving EFS24, and 9 (41%) relapsed with DLBCL, 13 (59%) relapsed with indolent lymphoma, and pathology was unknown in 4 patients. In the 47 patients who relapsed with DLBCL after achieving EFS24, 45% received intensive salvage chemotherapy, 19% received regular intensity chemotherapy, 9% received CNS directed chemotherapy, and 36% went on to receive autologous stem cell transplant (ASCT). In the 26 patients who relapsed with indolent lymphoma after achieving EFS24, 27% were initially observed, 54% received regular intensity chemotherapy, 4% received intensive salvage chemotherapy, and 19% received ASCT after subsequent progression. The median post-relapse survival (PRS) for all patients with a relapse after achieving EFS24 was 38.0 months (95% CI 27.5-48.5). The median PRS for patients who relapsed with DLBCL and indolent lymphoma after achieving EFS24 were 29.9 (19.9-39.9) and 89.9 (NR-NR) months, respectively (P=0.002; Figure 2). Conclusions: Relapses after achieving EFS24 in patients with DLBCL were uncommon in the rituximab era. Patient with DLBCL alone at diagnosis can relapse with either DLBCL or indolent lymphoma (3:1 ratio). Patients with concurrent DLBCL and indolent lymphoma at diagnosis had a significantly higher CIR, and relapses with DLBCL and indolent lymphoma were similar (2:3 ratio). Even with high intensity salvage chemotherapy and consolidative ASCT, patients who relapsed with DLBCL had a significantly worse survival compared to those who relapsed with indolent lymphoma. Late relapses with DLBCL remain clinically challenging, with a median survival of 2.5 years after relapse. Figure 1. Figure 1. Disclosures Maurer: Celgene: Research Funding; Nanostring: Research Funding; Morphosys: Research Funding. Witzig:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Ansell:Takeda: Research Funding; Pfizer: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; Seattle Genetics: Research Funding; Celldex: Research Funding; LAM Therapeutics: Research Funding; Trillium: Research Funding; Merck & Co: Research Funding; Bristol-Myers Squibb: Research Funding. Cerhan:Celgene: Research Funding; Jannsen: Other: Scientific Advisory Board; Nanostring: Research Funding.

Successful in vivo purging of CD34-containing peripheral blood harvests in mantle cell and indolent lymphoma: evidence for a role of both chemotherapy and rituximab infusion

Blood ◽  
2000 ◽  
Vol 96 (3) ◽  
pp. 864-869 ◽  
Author(s):  
Michele Magni ◽  
Massimo Di Nicola ◽  
Liliana Devizzi ◽  
Paola Matteucci ◽  
Fabrizio Lombardi ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Stem Cell ◽  
Follicular Lymphoma ◽  
Mantle Cell Lymphoma ◽  
Cell Lymphoma ◽  
Bone Marrow Involvement ◽  
Hematopoietic Stem ◽  
Mantle Cell

Abstract Elimination of tumor cells (“purging”) from hematopoietic stem cell products is a major goal of bone marrow–supported high-dose cancer chemotherapy. We developed an in vivo purging method capable of providing tumor-free stem cell products from most patients with mantle cell or follicular lymphoma and bone marrow involvement. In a prospective study, 15 patients with CD20+ mantle cell or follicular lymphoma, bone marrow involvement, and polymerase chain reaction (PCR)–detectable molecular rearrangement received 2 cycles of intensive chemotherapy, each of which was followed by infusion of a growth factor and 2 doses of the anti-CD20 monoclonal antibody rituximab. The role of rituximab was established by comparison with 10 control patients prospectively treated with an identical chemotherapy regimen but no rituximab. The CD34+ cells harvested from the patients who received both chemotherapy and rituximab were PCR-negative in 93% of cases (versus 40% of controls;P = .007). Aside from providing PCR-negative harvests, the chemoimmunotherapy treatment produced complete clinical and molecular remission in all 14 evaluable patients, including all 6 with mantle cell lymphoma (versus 70% of controls). In vivo purging of hematopoietic progenitor cells can be successfully accomplished in most patients with CD20+ lymphoma, including mantle cell lymphoma. The results depended on the activity of both chemotherapy and rituximab infusion and provide the proof of principle that in vivo purging is feasible and possibly superior to currently available ex vivo techniques. The high short-term complete-response rate observed suggests the presence of a more-than-additive antilymphoma effect of the chemoimmunotherapy combination used.

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