Incorporating targeted therapy into conditioning regimen for patients undergoing autologous stem cell transplant (ASCT) for aggressive CD20 positive B-cell lymphoma has altered the natural history of the disease: A multivariate analysis of the prognostic factors

Abstract Double hit lymphoma (DHL), defined as B cell lymphoma with a c-MYC rearrangement plus a IGH/BCL2 rearrangement, confers a poor prognosis. Outcomes with R-CHOP are dismal with reported 2 year EFS <30% in multiple series. To improve upon these results, Burkitt type regimens such as R-HyperCVAD and dose adjusted (DA) R-EPOCH have been attempted, but 2 year EFS remains < 50% in early reports. In addition, the SWOG-9704 study found a benefit for consolidative autologous stem cell transplant (autoSCT) in high risk DLBCL, likely including some DHL, although this reported benefit has not been confirmed in three other randomized European studies. Since 2010 the treatment algorithm at Oregon Health & Science University for fit patients with DHL has been DA-R-EPOCH followed by consolidative autoSCT in responding patients. Here we report the first 16 patients treated with consolidative autoSCT. At diagnosis, the median age was 58, and the median IPI was 3. All patients had rearrangements of c-MYC and IGH/BCL2. One of the c-MYC rearrangements was a classical t(8;14); the translocation partners in the other cases were unknown. Three patients also had a ‘triple hit’ with an additional BCL6 rearrangement. Fourteen patients received DA-R-EPOCH with intrathecal prophylaxis for induction. One received R-CHOP at another institution, and one received R-HyperCVAD. 15 of 16 patients were in CR after induction. Stem cell mobilization was performed with G-CSF +/- plerixafor, and BEAM was utilized as the high dose conditioning regimen. With a median follow-up of 18 months, the estimated 2 year PFS is 91 %, and the 2 year OS is 91 % in the 16 patients who underwent consolidative autoSCT. There were no deaths from non-relapse mortality, and the only relapse was 6 months post-transplant. All other patients undergoing autoSCT remain alive and in remission. An additional 15 patients also underwent induction with DA-R-EPOCH but did not proceed to autoSCT. Four patients who had intended to undergo autoSCT were refractory to induction. Of the remaining 11 patients, 9 did not pursue autoSCT because of age and/or comorbidities, and 1 each declined out of personal preference or insurance denial. Four of these 11 have relapsed or died. Our results suggest that consolidative autoSCT, especially after DA-R-EPOCH induction, is an effective treatment strategy for DHL in fit patients and should be explored in prospective studies. Disclosures No relevant conflicts of interest to declare.

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Maintenance rituximab after autologous stem cell transplant for high-risk B-cell lymphoma induces prolonged and severe hypogammaglobulinemia

Bone Marrow Transplantation ◽

10.1038/sj.bmt.1704742 ◽

2004 ◽

Vol 35 (2) ◽

pp. 207-208 ◽

Cited By ~ 39

Author(s):

S H Lim ◽

Y Zhang ◽

Z Wang ◽

W V Esler ◽

D Beggs ◽

...

Keyword(s):

Stem Cell ◽

High Risk ◽

B Cell ◽

Stem Cell Transplant ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Autologous Stem Cell Transplant ◽

Cell Transplant

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ALK-negative anaplastic lymphoma after autologous stem cell transplant for relapsed diffuse large B-cell lymphoma

Leukemia Research ◽

10.1016/j.leukres.2010.11.018 ◽

2011 ◽

Vol 35 (6) ◽

pp. e59-e60 ◽

Cited By ~ 1

Author(s):

Seah H. Lim ◽

Joseph M. Guileyardo ◽

Robbie Graham ◽

Lorna R. Strong ◽

William V. Esler

Keyword(s):

Stem Cell ◽

B Cell ◽

Stem Cell Transplant ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Autologous Stem Cell Transplant ◽

Cell Transplant ◽

Anaplastic Lymphoma ◽

Large B Cell Lymphoma ◽

Large B Cell

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Progression-free survival at 24 months as a landmark after autologous stem cell transplant in relapsed or refractory diffuse large B-cell lymphoma.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.7522 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 7522-7522

Author(s):

Aung M. Tun ◽

Seth Maliske ◽

Yucai Wang ◽

Matthew J. Maurer ◽

Ivana N. M. Micallef ◽

...

Keyword(s):

Stem Cell ◽

Stem Cell Transplant ◽

Cell Lymphoma ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

Autologous Stem Cell Transplant ◽

Cell Transplant ◽

Free Survival ◽

Large B Cell Lymphoma ◽

Large B Cell

7522 Background: Patients with newly diagnoseddiffuse large B-cell lymphoma (DLBCL) who achieve event-free survival at 24 months (EFS24) following immunochemotherapy (IC) have excellent overall survival (OS) similar to that of age- and sex-matched general population. The standard of care for patients with relapsed or refractory (RR) DLBCL following frontline IC is salvage therapy followed by autologous stem cell transplant (ASCT). The goal of this study is to evaluate the role of progression-free survival (PFS) at 24 months (PFS24) as a landmark after ASCT in patients with RR DLBCL. Methods: Patients with RR DLBCL after frontline R-CHOP or R-CHOP-like IC who underwent salvage therapy and ASCT at Mayo Clinic or University of Iowa between 07/2000 and 4/2020 were identified from institutional lymphoma transplant databases. Clinical characteristics, treatment information, and outcome data were abstracted. Post-ASCT PFS, OS, and post-relapse survival (PRS) were plotted by Kaplan-Meier method, and cumulative incidences of relapse vs non-relapse mortality (NRM) and different causes of death were compared accounting for competing events. Statistical analyses were performed in EZR v1.54. Results: A total of 437 patients were identified. Median age at ASCT was 61 years (range 19-78), and 280 (64%) were male. After a median post-ASCT follow up of 8.0 years (95% CI 7.2-8.7), 215 patients had a relapse (or disease progression), 180 within 2 years and 35 after 2 years. For the entire cohort, post-ASCT relapse rate was much higher than NRM rate (48.1 vs 9.1% at 5-year). Median PFS and OS after ASCT was 2.7 and 5.4 years, respectively. Lymphoma was the primary cause of death after ASCT. In contrast, for patients who had achieved PFS24 (n = 220), rates of post-PFS24 relapse and NRM were similar (14.8% and 12.3% at 5-year). Median PFS and OS after achieving PFS24 was 10.0 and 11.5 years, respectively. Lymphoma related and unrelated death rates were similar after achieving PFS24 (Table). For all patients who had a post-ASCT relapse, median PRS was 0.7 years (95% CI 0.5-0.9), and late relapse ( > 2 vs ≤2 years after ASCT) was associated with better PRS (median 2.3 [1.7-4.8] vs 0.5 [0.3-0.7] years, p < 0.001). Conclusions: Post-ASCT PFS24 is an important prognostic predictor of post-ASCT outcomes in patients with RR DLBCL following frontline IC.[Table: see text]

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Autologous Stem Cell Transplant in Recurrent Diffuse Large B- Cell Lymphoma: Prior Rituximab Therapy Has No Impact On Early Lymphocyte Recovery and Transplant Outcome.

Blood ◽

10.1182/blood.v114.22.3407.3407 ◽

2009 ◽

Vol 114 (22) ◽

pp. 3407-3407

Author(s):

Daniel G Stover ◽

Vishruth K Reddy ◽

John P. Greer ◽

Madan Jagasia ◽

David Morgan ◽

...

Keyword(s):

Stem Cell ◽

B Cell ◽

Salvage Therapy ◽

Stem Cell Transplant ◽

Conditioning Regimen ◽

B Cell Lymphoma ◽

Disease Status ◽

Autologous Stem Cell Transplant ◽

Cell Transplant ◽

Transplant Outcome

Abstract Abstract 3407 Poster Board III-295 Background: Diffuse Large B Cell (DLBCL) is the most common histological subtype of lymphoma diagnosed in the United States. Following failure with standard Rituximab- CHOP chemotherapy, salvage therapy followed by autologous stem cell transplant is the standard treatment for those who are transplant eligible. Previous data suggest that early lymphocyte recovery is associated with superior survival after autologous stem cell transplantation (ASCT) in lymphoma. However, there are no consistent data on whether prior rituximab therapy affects lymphocyte recovery early post- transplantation. In this study we present our transplant outcome experience regarding early lymphocyte recovery in patients exposed to prior rituximab therapy. Methods: One hundred fifteen patients undergoing autologous stem cell transplant for relapsed DLBCL at a single institution between January 2000 and December 2008 were included in our analysis after obtaining IRB approval. Descriptive statistics, Wilcoxon signed rank sum test and Kaplan-Meier analysis were performed as required using SPSS software. Results: Median age of patients undergoing ASCT was 50 years (range: 24-69 years). Nine patients who underwent ASCT for transformed DLBCL and 7 patients with T-cell rich B cell lymphoma were also included in the final analysis. Six patients had stage I disease, 29 patients with stage II, 33 patients with stage III and 36 patients were diagnosed with stage IV. Thirteen patients had bulky retroperitoneal adenopathy at the time of original diagnosis. Seventy one (66.3%) patients received one salvage therapy prior to transplant. Thirty six (33.7%) patients received two or more salvage therapies prior to transplant. Mobilization data was available on 89 patients. Of those, 82 patients were mobilized with chemotherapy and 5 patients underwent mobilization with GCSF alone. High dose cytclophosphamide (7200 mg/sq.m), etoposide (2000 mg/sq.m) and BCNU (400 mg/sq.m) [CBV] was the conditioning regimen in 88 (77.2%) patients. Sixty eight (59.6%) patients received pretransplant rituximab therapy. Sixty one (61.6%) patients were in radiographic complete response (CR) following salvage therapy at the time of transplant. Sixty nine (78.4%) patients continued to be in CR at day 100 evaluation. Nineteen (21.6%) patients had persistent disease requiring further therapy. The median survival of all patients was 38.7 months (range: 3 months- 186 months). At the time of the analysis, 69 (60.5%) patients were still alive. Prior rituximab therapy did not affect lymphocyte recovery on day 14 (p=0.95) or day 28 (p=0.27). Lymphocyte recovery on day 14 and day 28 (continuous and categorical variables) had no impact on transplant outcome. Other factors such as age, disease stage at presentation, presence of bulky retroperitoneal nodal disease, number of regimens, mobilization procedure, type of conditioning regimen, pre-transplant radiation therapy, pre-transplant disease status (CR vs. PR in chemo sensitive disease) had no impact on survival. Conclusions: our data demonstrate that prior rituximab therapy has no impact on lymphocyte recovery on day 14 or day 28. In this group of patients, lymphocyte recovery did not impact on autologous stem cell transplant outcome. The survival benefit with early lymphocyte recovery as mentioned in prior reports may be lost with longer follow up. Prior rituximab therapy may mitigate the effect of the number of treatment regimens or disease status (CR vs. PR) on transplant outcome. Disclosures: No relevant conflicts of interest to declare.

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