scholarly journals Durable Remissions Achieved with R-CHOP Chemotherapy without Radiotherapy in Patients with Primary Mediastinal B-Cell Lymphoma - the Royal Marsden Experience

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4240-4240
Author(s):  
Vasiliki Michalarea ◽  
Dima El-Sharkawi ◽  
Siraj Yusuf ◽  
Mary Gleeson ◽  
Laura Hickmott ◽  
...  
Keyword(s):  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Salvage Chemotherapy ◽  
Advisory Board ◽  
The Other ◽  
Chop Chemotherapy ◽  
Consolidation Radiotherapy ◽  
Pet Scans

Abstract Introduction: Primary mediastinal B Cell Lymphoma (PMBL) is a high-grade non-hodgkin lymphoma with distinct clinical and biological features. Optimal chemotherapy for this lymphoma is not established but some centres favour more intensive regimes such as DA EPOCH-R over R-CHOP. The role of consolidation radiotherapy is yet to be clarified and whether it can be omitted in those patients with a negative end-of-treatment PET scan (EOT PET) regardless of induction chemotherapy. Furthermore, the occurrence of false positive EOT PET scans may lead to overtreatment. The aim of this study was to establish the outcomes of patients (pts) with PMBL who had been treated in a single centre. Methods: Pts diagnosed with PMBL between 2003 and 2015 in Royal Marsden Hospital were included. Data was collected from electronic patient records and PET CT images review. Survival was defined from date of diagnosis until date of death or date of last follow up. Results: Thirty-four pts were identified with characteristics as shown in the table. Median diameter of the mediastinal mass was 12cm (range 5.5 - 24cm); 25 (74%) pts had a mass of ≥ 10cm. The majority of pts received R-CHOP chemotherapy (2 had 14 day cycles, 30 had 21 day cycles), 1 R-GCVP and another R-PACEBOM. Median number of cycles of chemotherapy was 6 (range 1-8). Seven out of 32 (22%) pts received involved field radiotherapy (IFRT). EOT PET was available for 30 pts. Median time to obtaining EOT PET from completion of chemotherapy was 31 days (20-81). Twenty-three out of 30 pts had EOT PET negative disease with a Deauville score (DS) of 1-3. Twenty-one of these 23 pts did not receive IFRT. Two of these 21 pts relapsed in the mediastinum and were treated with salvage chemotherapy followed by autologous stem cell transplant (ASCT) of whom 1 died due to their lymphoma. The 2 patients who received consolidation radiotherapy remain in remission. Seven out of 30 pts had a positive EOT PET (DS 4-5); of whom 5 received IFRT. Two out of 5 patients relapsed and proceeded with further chemotherapy of whom 1 died due to treatment-related causes while the other 4 patients were alive at time of last follow-up. Two pts with a positive EOT PET did not have IFRT, 1 proceeded with salvage chemotherapy but died due to lymphoma and the other patient was followed up with serial PET scans and ultimately the residual avidity was considered to be due to thymic hyperplasia. Conclusion: Our analysis demonstrates that for the 23 patients who achieved a complete metabolic response on EOT PET the risk of relapse was low (9%) (despite that only 2 patients received consolidation radiotherapy) and only one patient (4%) died of lymphoma. Thus the majority of patients with a negative EOT PET scan following R-CHOP chemotherapy may not need consolidation radiotherapy. This finding should be taken into account when considering the risk/benefit of adding radiotherapy treatment to patients who are already in metabolic CR after chemotherapy. Consolidation radiotherapy is currently being investigated in a prospective IELSG37 trial, NCT01599559. Table. Table. Disclosures Chau: Eli-Lilly: Honoraria, Other: Advisory Board, Research Funding; Bristol Meyers Squibb: Other: Advisory Board; MSD: Other: Advisory Board; Bayer: Other: Advisory Board; Roche: Other: Advisory Board; Merck Serono: Other: Advisory Board, Research Funding; Five Prime Therapeutics: Other: Advisory Board; Astra-Zeneca: Other: Advisory Board; Janssen-Cilag: Research Funding; Sanofi Oncology: Research Funding. Cunningham:Roche pharmaceuticals: Research Funding.

scholarly journals Maintenance Rituximab Following R-CHOP Chemotherapy in Patients with Composite or Discordant, Indolent and Aggressive, B-Cell Non-Hodgkin Lymphomas

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3950-3950
Author(s):  
Roopesh R. Kansara ◽  
Joseph M. Connors ◽  
Kerry J. Savage ◽  
David W Scott ◽  
Randy D. Gascoyne ◽  
...  
Keyword(s):  
B Cell ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Performance Status ◽  
B Cell Lymphoma ◽  
Advisory Board ◽  
Low Grade ◽  
Treatment Policy ◽  
The Impact

Abstract Background: Patients with follicular lymphoma (FL) who achieve a complete (CR) or partial (PR) response to rituximab-containing chemotherapy followed by maintenance rituximab (MR) experience improved progression-free survival (PFS). In contrast, MR does not improve outcomes in chemo-sensitive patients with diffuse large B-cell lymphoma (DLBCL). There are no published data describing the impact of MR in patients presenting with indolent and aggressive histology lymphoma simultaneously in the same biopsy (composite, COM) or two separate sites (discordant, DIS). Methods: Patients with newly-diagnosed COM/DIS lymphomas composed of an indolent B-cell non-Hodgkin lymphoma (excluding CLL/SLL, mantle cell lymphoma, and grade 3B FL) and DLBCL were identified in the British Columbia Cancer Agency Lymphoid Cancer Database. All patients received first-line chemotherapy with R-CHOP. In early 2006, a treatment policy was introduced recommending MR 375 mg/m2 IV every 3 months for 2 years in patients with COM/DIS lymphomas achieving a CR/PR to R-CHOP induction. PFS, time to progression (TTP) and overall survival (OS) were calculated from the time of diagnosis and compared between treatment groups. Results: 98 patients with COM/DIS lymphomas were identified between January 2001 and December 2013: median age 64 y (range 22 - 86), 56% male, 48% elevated LDH, 30% performance status ≥ 2, 87% stage III/IV, and 51% high-intermediate or high IPI. 58 (59%) and 40 (41%) patients had COM and DIS lymphoma, respectively. FL was the indolent component in 65% of all cases. 35/40 patients with DIS had low-grade histology in the bone marrow. Following R-CHOP, 77 (79%) and 21 (21%) patients achieved CR and PR, respectively. 43 patients were treated with R-CHOP alone before the MR policy introduction, and 55 were treated with R-CHOP+MR; the latter group received a median of 8 (range 1 - 8) MR doses. There were no significant differences in baseline characteristics or response rates between the two groups with the exception of a higher proportion of patients with poor performance status in the group not given MR. With a median follow-up of 10y (range 1.5 - 13.6) in living patients treated with R-CHOP and 6y (range 0.9-9.5) in patients treated with R-CHOP+MR, there were 20 (47%) and 15 (27%) relapses, respectively (p=0.26). Of these, 11 relapsed with indolent histology, 11 relapsed with DLBCL, 3 relapsed in the central nervous system (CNS), and 10 had no biopsy at relapse (8 had aggressive and 2 indolent clinical behavior on review of medical records). There were 6 (30%) indolent and 14 (70%) aggressive relapses in patients treated with R-CHOP, while there were 7 (47%) indolent and 8 (53%) aggressive relapses in patients treated with R-CHOP+MR (p=0.31). 19 patients eventually died from lymphoma (8 with DLBCL relapse, 5 without a biopsy at relapse, and all 3 with CNS recurrence). The 6-y PFS was 60% (standard error [SE] 5%) with no difference between patients treated with or without MR (Hazard ratio (HR) 0.74, 95% CI 0.39 - 1.37, p= 0.33). The 6-year TTP was 64% (SE 5%), again with no differences between the two groups (HR 0.68, 95% CI 0.34 - 1.33, p= 0.25). The 6-year OS was similar between the two groups (p= 0.89). In the subgroup of patients with FL (21 R-CHOP and 43 R-CHOP+MR) the addition of MR did not impact PFS (p= 0.90), TTP (p= 0.99), or OS (p=0.55). An additional 52 patients were diagnosed after the treatment policy introduction in 2006, but did not receive MR for several reasons including physician non-adherence, progressive disease on R-CHOP, toxicity from R-CHOP or patient refusal. In an intent-to-treat analysis (43 pre-policy and 107 post-policy) there were no differences in outcomes. In a per-protocol analysis (95 R-CHOP and 55 R-CHOP+MR), there were no significant differences in outcomes. Conclusion: The addition of MR does not appear to improve PFS, TTP or OS in patients with COM/DIS lymphomas achieving CR/PR to R-CHOP, although comparisons are likely underpowered and 6-year median length of follow-up in the MR group may not be sufficient. However, the majority (63%) of relapses are aggressive and unlikely to be impacted by MR. The role of MR in these uncommon lymphomas requires further exploration. Disclosures Connors: Roche: Research Funding; Seattle Genetics: Research Funding. Savage:Seattle Genetics: Honoraria, Speakers Bureau; BMS: Honoraria; Infinity: Honoraria; Roche: Other: Institutional research funding. Scott:Celgene: Consultancy, Honoraria; NanoString: Patents & Royalties: Inventor on a patent that NanoString has licensed. Gerrie:Roche: Honoraria, Other: Advisory board, Research Funding; Lundbeck: Honoraria, Other: Advisory board, Research Funding; Janssen: Other: Advisory board. Villa:Roche: Research Funding.

scholarly journals Burden of Illness and Outcomes in the 2nd Line Treatment of Large B-Cell Lymphoma: A Real-World Comparison of Medicare Beneficiaries with and without Stem Cell Transplants

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 1-2
Author(s):  
Karl M Kilgore ◽  
Anny C Wong ◽  
Julia Thornton Snider ◽  
Paul Cheng ◽  
Amy Schroeder ◽  
...  
Keyword(s):  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Salvage Chemotherapy ◽  
Publicly Traded ◽  
Large B Cell Lymphoma ◽  
Line Therapy ◽  
Preparative Regimen ◽  
Baseline Characteristics

Introduction: Standard first line therapy (LOT) for patients (pts) with large B-cell lymphoma (LBCL) involves chemotherapy with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) or a similar regimen, e.g. R-CHOP with the addition of etoposide (R-EPOCH). While most pts respond, 30-40% of pts relapse or fail to achieve remission with 1st LOT. For those pts, the goal of curative 2nd LOT is typically platinum-based salvage chemotherapy in preparation for autologous stem cell transplant (ASCT). However, many pts (50% or more) do not qualify for intensive therapy, either due to age or comorbidities, or because they do not respond to or cannot tolerate salvage chemotherapy. For those further treatment options are limited. Objectives: In a sample of U.S. LBCL pts 65 and older, who have progressed to 2nd LOT and are eligible for ASCT, to compare the patient characteristics, treatments, costs and overall survival between pts who received SCT with those who did not. Methods: This retrospective cohort study used 100% Medicare Fee-for-Service Parts A/B claims data and Part D Prescription Drug Event data to identify pts ≥ 65 years of age, newly diagnosed with LBCL in 2012-2017, and who had ≥ 6 months continuous enrollment pre-diagnosis (baseline) and ≥ 12 months post-diagnosis, or who died after initiation of 2nd LOT. All were treated with a CHOP-like regimen 1st LOT and progressed to 2nd LOT. Eligible pts who received a 2nd LOT with a SCT-preparative regimen per NCCN guidelines were stratified into the "ASCT-intended" cohort, and the remainder into the "ASCT-not-intended" cohort. The ASCT-intended group was further subset into those who received a SCT and those who did not (Non-SCT). These 2 subsets formed the primary comparison groups. Baseline characteristics were age, gender, race, dual eligibility status (i.e. Medicare plus Medicaid), and Charlson-Deyo Comorbidity Index (CCI). Measures of utilization during follow-up (from initiation of 2nd LOT to loss to follow-up) were hospitalizations, outpatient and emergency department (ED) visits, and post-acute care. Costs during follow-up reflected standardized, inflation-adjusted, all-cause paid amounts. Utilization and cost metrics were standardized to per-patient-per-month (PPPM). Overall survival (OS) was measured from the start of 2nd LOT until death, disenrollment or the end of the study period. Results: 4,758 pts met all inclusion criteria. 3,713 (78%) did not receive a SCT-preparative regimen after 1st LOT. 1,045 pts (22%) received a SCT-preparative regimen and constituted the ASCT-intended group. Of these, 244 (23.3%) received a SCT and 801 (76.7%) did not. The remainder of this report focuses on a comparison of the SCT and non-SCT cohorts. Baseline characteristics, treatments, utilization and cost are summarized in Table 1. Both groups were predominantly white, but SCT pts were, on average, 5 years younger, slightly more likely to be male, and had slightly lower mean CCI scores. 13.1% of non-SCT pts were dual eligible vs. 4.5% of SCT (all p < .01 except Race). 93.9% of SCT procedures were autologous, and no pts had more than 1 SCT during follow-up. Non-SCT pts had higher all-cause utilization for all categories except for acute hospitalizations. The higher inpatient utilization for the SCT group may reflect the SCT procedure itself (94% of SCT were inpatient). A similar pattern was observed in the cost data, where Non-SCT pts incurred higher costs except for acute hospitalizations. Results for OS are summarized in Figure 1. Non-SCT pts had significantly lower rates of survival than SCT pts. 94.7% of SCT pts were still alive 6 months after initiation of 2nd LOT, whereas only 66.9% of non-SCT pts were. At two years post-2nd LOT, survival rates were 69.7% vs. 36.3%. Conclusions: In this study, only 23.3% of SCT-intended pts ultimately received it. The remaining 76.7% were SCT-intended but never received a transplant. Compared to the SCT pts, the non-SCT pts were older, had more comorbidities, had higher rates of healthcare utilization and costs post-2nd line therapy in all categories (except acute inpatient), and lower OS. 38.7% of non-SCT pts proceeded to additional lines of lymphoma-directed therapies beyond 2nd line, which may suggest that their clinicians felt that there was potential benefit to further treatment. These data suggest there may be unmet need for elderly pts with LBCL who are eligible for ASCT, but do not ultimately receive it. Disclosures Kilgore: Kite, A Gilead Company: Research Funding. Wong:Kite, A Gilead Company: Research Funding. Thornton Snider:Precision Medicine Group: Ended employment in the past 24 months, Research Funding; Gilead Sciences: Current equity holder in publicly-traded company, Research Funding; Kite, A Gilead Company: Current Employment. Cheng:Kite, A Gilead Company: Current Employment; Gilead Sciences: Current equity holder in publicly-traded company. Schroeder:Kite, A Gilead Company: Research Funding. Mohammadi:Kite, A Gilead Company: Research Funding.

10 Years Follow-up of the GELA LNH98.5 Study, First Randomized Study Comparing R-CHOP to CHOP Chemotherapy in Patients with Diffuse Large B-Cell Lymphoma.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3741-3741 ◽  
Author(s):  
Bertrand Coiffier ◽  
Christian Gisselbrecht ◽  
Andre Bosly ◽  
Raoul Herbrecht ◽  
Reda Bouabdallah ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Randomized Study ◽  
B Cell Lymphoma ◽  
Chop Chemotherapy ◽  
Advisory Committees ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 3741 Poster Board III-677 LNH98.5 was the first randomized study with the addition of rituximab to CHOP in patients with diffuse large B-cell lymphoma. 399 patients were randomized, 197 in CHOP arm and 202 in R-CHOP arm. Patients were aged between 60 and 80 years (median 70 years), had disease stage II to IV, and no contra-indication to one of the drugs. 60% had poor risk lymphoma according to IPI. Response to treatment and early survival analyses were previously presented with 2 years and 5 years median follow-up (NEJM 2002;346:235 and JCO 2005;23:4117). With a median follow-up of 10 years, median age of surviving patients is 78 years, oldest patient being 91 years old. Only 4 patients were lost for follow-up, defined as not seen during the last 18 months, at 5, 7, 8, and 8 years. No event was observed in 105 of the 399 patients, 37 (19%) in CHOP arm and 68 (34%) in R-CHOP arm. Relapse was observed in 73 (59%) and 51 (34%) of CR patients, and death without progression in 16 and 33 patients, respectively. Death occurred in 71% and 56% of the patients, most of them from disease progression but 21 and 20 cancers were observed, representing half of the deaths without progression. Most frequent cancers were colon and lung; two MDS were observed in CHOP arm and one AML in R-CHOP arm. One patient with CHOP presented a multiple myeloma 10 years after DLBCL. During the last 3 years, 10 additional patients relapsed, 4 in CHOP arm and 6 in R-CHOP arm, these late relapses representing 4% of CR patients. Median overall survival was 37 months in CHOP arm and 7 y 9 m in R-CHOP arm with 10-y survival of 28% and 43%, respectively (p<0.001). Median survival from progression was 8 months in both arms. This analysis showed that the benefit of combining rituximab with CHOP chemotherapy persists with a median follow-up of 10 years and that over 40% of elderly patients are alive 10 years later confirming these patients could express long-term survival if treated like younger patients. However, late relapses do occur and new strategies should be developed to prolong the response of these patients. Disclosures: Coiffier: Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Gisselbrecht:Roche: Research Funding, Speakers Bureau. Bosly:Roche: Research Funding, Speakers Bureau. Herbrecht:Roche: Research Funding. Bouabdallah:Roche: Research Funding. Morel:Roche: Research Funding. Van Den Neste:Roche: Research Funding. Bordessoule:Roche: Research Funding. Haioun:Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Tilly:Roche: Research Funding, Speakers Bureau. Salles:Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau.

scholarly journals Hemophagocytic Lymphohistiocytosis in Adults (aHLH): Results from the German HLH Registry

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2523-2523 ◽  
Author(s):  
Sebastian Birndt ◽  
Thomas Schenk ◽  
Frank M. Brunkhorst ◽  
Georg Maschmeyer ◽  
Frank Rothmann ◽  
...  
Keyword(s):  
Diagnostic Criteria ◽  
Hemophagocytic Lymphohistiocytosis ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Case Series ◽  
B Cell Lymphoma ◽  
Compound Heterozygous ◽  
Cytokine Release ◽  
Laboratory Findings

Abstract Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a severe hyperinflammatory syndrome caused by excessive immune activation leading to a life-threatening pro-inflammatory cytokine storm. HLH is not an entity of its own, but a clinical syndrome triggered by various conditions like infections, malignancy or autoimmune disorders. HLH pathogenesis is complex and still not fully understood. Contributing factors include immunosuppression (chemotherapy, long-term immunosuppressive therapy), cytokine release from tumor cells, imbalance between infected and immune effector cells as well as genetic predisposition. Despite improved HLH-specific therapy (adapted components from the pediatric HLH-1994 protocol), prognosis is still poor among adult HLH patients. Due to the lack of data on adult HLH in Germany, a national multicenter registry (http://www.hlh-registry.org/) was initiated. Methods: Patients (pts) with proven or suspected HLH were registered by 35 institutions across Germany from August 2010 to July 2016. Both HLH-2004 diagnostic criteria and the HScore (www.saintantoine.aphp.fr/score/) were used to confirm HLH diagnosis. To characterize adult HLH patients, data referring to underlying disease, treatment, outcome, clinical manifestations and laboratory findings were recorded. Where available, patient samples were tested for mutations of the perforin gene PRF1 by standard Sanger sequencing. Results: A total of 125 pts (48 female) were enrolled in our registry, of whom 105 pts either fulfilled diagnostic criteria according to HLH-2004 diagnostic guidelines (n=96) or met at least 4 out of 8 criteria and reached HLH-probability of over 90 % in the HScore (n=9). Among these 105 pts, n=38 (36 %) were female and n=67 (64 %) male. Median age at diagnosis was 49 years (range 17 - 81). Trigger diseases were in line with the literature, with infections (n=34) and malignancy (n=40) being most frequent (Table 1). Patients show a wide spectrum of underlying conditions, i.e. allogeneic stem cell transplantation (alloSCT) or HLH-mimicking diseases due to cytokine release in response to blinatumomab therapy. Late onset hereditary HLH was found in 3 pts (XLP-1 and -2 respectively in EBV-coinfected pts, one pt with perforin mutation - see below). 22 of 105 patients (21 %) were tested for PRF1 mutations. A compound heterozygous PRF1 A91V/Q405X mutation was identified in one pt presenting with NK/T-cell lymphoma. Heterozygous PRF1 A91V mutations were found in 2 pts with B-cell lymphoma and HLH following alloSCT respectively, in one case with available buccal swab DNA to prove germline origin of the mutation. Table 2 summarizes clinical and laboratory findings in the cohort. A median ferritin value of 32,000 µg/L underlines the importance to evaluate pts with highly elevated ferritin with respect to potential HLH diagnosis. Apart from fever and splenomegaly, clinical presentation frequently comprised hepatomegaly, liver failure, hyperbilirubinemia, renal failure, lung involvement like ARDS, or bleeding. Treatment included steroids in the vast majority of pts (n=89), often combined with i.v. immunoglobulins (n=47) and etoposide (n=49). After a median follow up time of 164 days, 48/97 pts (49.5 %) were alive, 8 pts were lost to follow up. Survival analysis revealed median overall survival of 454 days (Figure 1a). Comparing malignancy-associated HLH and HLH after alloSCT with infection- and autoimmune-associated HLH or HLH due to unknown triggers, survival was significantly poorer in the malignancy/alloSCT group (Figure 1b). Conclusions: HLH trigger conditions in adult patients in Germany are in accordance with published case series. Outcome in adult HLH is still poor, with malignancy-associated and HLH after alloSCT showing the worst prognosis. Diagnostic vigilance and early treatment is a prerequisite for improving outcome of adult HLH. In particular, high ferritin values should raise suspicion of HLH. Disclosures Hochhaus: Pfizer: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; BMS: Honoraria, Research Funding; ARIAD: Honoraria, Research Funding.

scholarly journals Impact of Interim FDG-PET (iPET) in the Outcomes of Patients with Aggressive B-Cell Lymphomas Receiving DA-EPOCH-R

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2898-2898
Author(s):  
Vania Phuoc ◽  
Leidy Isenalumhe ◽  
Hayder Saeed ◽  
Celeste Bello ◽  
Bijal Shah ◽  
...  
Keyword(s):  
B Cell ◽  
Board Of Directors ◽  
Fdg Pet ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Advisory Committees ◽  
End Of Treatment

Introduction: 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET) remains the standard of care for baseline and end of treatment scans for aggressive non-Hodgkin lymphomas (NHLs). However, the role of interim FDG-PET remains not as well defined across aggressive NHLs, especially in the era of high-intensity chemoimmunotherapy. Interim FDG-PET (iPET) can serve as an early prognostic tool, and prior studies evaluating the utility of iPET-guided treatment strategies primarily focused on diffuse large B-cell lymphomas (DLBCL) and frontline R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Classification criteria systems assessing response also differ between studies with no clear consensus between use of Deauville criteria (DC), International Harmonization Project (IHP), and the ΔSUVmax method. Methods: This study evaluates our institutional experience with iPET during treatment with DA-EPOCH ± R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin with or without Rituximab) in aggressive NHLs. We retrospectively evaluated 70 patients at Moffitt Cancer Center who started on DA-EPOCH ± R between 1/1/2014 to 12/31/2018 for aggressive NHLs. Response on interim and end-of-treatment (EOT) scans were graded per DC, IHP, and ΔSUVmax methods, and progression free survival (PFS) probability estimates were calculated with chi-square testing and Kaplan Meier method. PFS outcomes were compared between interim negative and positive scans based on each scoring method. Outcomes were also compared between groups based on interim versus EOT positive or negative scans. Results: We identified 70 patients with aggressive NHLs who received DA-EPOCH ± R at our institute. The most common diagnoses were DLBCL (61%) followed by Burkitt's lymphoma (10%), primary mediastinal B-cell lymphoma (9%), plasmablastic lymphoma (7%), gray zone lymphoma (6%), primary cutaneous large B-cell lymphoma (1%), primary effusion lymphoma (1%), and other high-grade NHL not otherwise specified (3%). Of the 43 patients with DLBCL, 21/43 (49%) had double hit lymphoma (DHL) while 7/43 (16%) had triple hit lymphoma (THL), and 3/43 (7%) had MYC-rearranged DLBCL while 2/43 (5%) had double expressor DLBCL. Thirty nine out of 70 (56%) were female, and median age at diagnosis was 58.39 years (range 22.99 - 86.86 years). Most patients had stage IV disease (49/70, 70%), and 43/70 (61%) had more than one extranodal site while 45/70 (64%) had IPI score ≥ 3. Forty-six out of 70 (66%) received central nervous system prophylaxis, most with intrathecal chemotherapy (44/70, 63%). Fifty-five out of 70 (79%) had iPET available while 6/70 (9%) had interim computerized tomography (CT) scans. Fifty-six out of 70 (80%) had EOT PET, and 4/70 (6%) had EOT CT scans. Sustained complete remission occurred in 46/70 (66%) after frontline DA-EPOCH ± R (CR1), and 12/70 (17%) were primary refractory while 5/70 (7%) had relapse after CR1. Four of 70 (6%) died before cycle 3, and 3/70 (4%) did not have long-term follow-up due to transition of care elsewhere. Median follow-up was 15.29 months (range 0.85 - 60.09 months). There was significantly better PFS observed if iPET showed DC 1-3 compared to DC 4-5 (Χ2=5.707, p=0.0169), and PFS was better if iPET was negative by IHP criteria (Χ2=4.254, p=0.0392) or ΔSUVmax method (Χ2=6.411, p=0.0113). Comparing iPET to EOT PET, there was significantly better PFS if iPET was negative with EOT PET negative (iPET-/EOT-) compared to iPET positive with EOT negative (iPET+/EOT-), and iPET+/EOT+ and iPET-/EOT+ had worse PFS after iPET-/EOT- and iPET+/EOT- respectively. This pattern in iPET/EOT PFS probability remained consistent when comparing DC (Χ2=30.041, p<0.0001), IHP (Χ2=49.078, p<0.0001), and ΔSUVmax method (Χ2=9.126, p=0.0104). These findings fit clinical expectations with positive EOT scans indicating primary refractory disease. There was no significant difference in PFS when comparing DLBCL versus non-DLBCL (Χ2=3.461, p=0.0628) or DHL/THL versus non-DHL/THL diagnoses (Χ2=2.850, p=0.0914). Conclusion: Our findings indicate a prognostic role of iPET during treatment with DA-EPOCH ± R for aggressive NHLs. Significant differences in PFS were seen when graded by DC, IHP, and ΔSUVmax methods used in prior studies and when comparing interim versus EOT response. Larger studies are needed to confirm these findings. Disclosures Bello: Celgene: Speakers Bureau. Shah:Novartis: Honoraria; AstraZeneca: Honoraria; Spectrum/Astrotech: Honoraria; Adaptive Biotechnologies: Honoraria; Pharmacyclics: Honoraria; Jazz Pharmaceuticals: Research Funding; Incyte: Research Funding; Kite/Gilead: Honoraria; Celgene/Juno: Honoraria. Sokol:EUSA: Consultancy. Chavez:Janssen Pharmaceuticals, Inc.: Speakers Bureau; Genentech: Speakers Bureau; Kite Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees.

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.

High Incidence of False Positive PET Scans in Patients with Aggressive Non-Hodgkins Lymphoma Treated with Rituximab-Containing Regimens.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 2401-2401
Author(s):  
Hyo S. Han ◽  
Maricer P. Escalon ◽  
Aldo Serafini ◽  
Izidore S. Lossos
Keyword(s):  
Ct Scan ◽  
Predictive Value ◽  
Cell Lymphoma ◽  
The Other ◽  
Non Hodgkins Lymphoma ◽  
Residual Masses ◽  
Therapy Completion ◽  
Pet Scans ◽  
Post Therapy

Abstract Introduction: 18F-Fluorodeoxyglucose positron emission tomography (PET) is increasingly used for initial staging and response assessment in patients with Non-Hodgkins lymphoma (NHL) and is a powerful predictor of relapse and survival in this setting. All reported PET studies, however, were performed in the pre-rituximab era. Little is known about the predictive abilities of PET in rituximab-treated patients. Patients and Methods: Patients with aggressive NHL treated at the University of Miami between September 2002 and January 2006 that had baseline and follow-up PET studies were included in the study. Clinical characteristics at presentation, PET and CT scan results, and outcomes were reviewed. PET studies were defined as positive if greater than physiological activity was observed. Results: A total of 33 patients with the following histologies were included: diffuse large B cell lymphoma (23 patients), Mantle-cell lymphoma (5), Peripheral T-cell lymphoma (3) and NK/T cell lymphoma (2). The median age was 54 years (range 21–92) and 19 were male (58%). Six patients had an IPI of 0, 13 an IPI of 1, 10 an IPI of 2, 3 an IPI of 3, and 1 an IPI of 4. All patients with CD 20+ lymphomas were treated with rituximab containing regimens. Median follow up was 18 months (range 6–47). All patients had positive PET scans at diagnosis. Nine of 25 (36%) mid-therapy PET studies were positive. Four of these patients exhibited persistent PET positivity, of which 2 eventually died of progressive disease. In the other 2 patients, disease recurrence was biopsy-proven in one patient, while the other received further chemotherapy and is presently alive and in CR. Upon therapy completion, the remaining 5 converted to negative studies and 4 of these patients are in continuous complete remission (CR) for 8 to 19 months. The fifth patient relapsed 6 month after treatment. The relapse positive predictive value (PPV), negative predictive value (NPV), sensitivity (Se) and specificity (Sp) of the mid-therapy PET were 55.5% (95% CI 23–85%), 81.2% (95% CI 53–95%), 62.5% (95% CI 26–90%), and 76.4% (95% CI 50–92%), respectively. Upon therapy completion, 5 patients with residual masses on CT scans had positive PET scans, including 2 patients with positive mid-therapy PET scans. Biopsy was performed in 1 and did not demonstrate lymphoma, 1 was followed-up for 10 months without evidence of disease and 3 demonstrated disease progression and were salvaged with additional therapy. Seven patients with a negative post-therapy PET demonstrated residual masses by CT scan criteria. Two of these patients relapsed while the remaining 5 are in CR for 8 to 19 months. In two of these patients in CR, PET scans performed 3 to 6 months after therapy completion became positive. However, biopsy revealed inflammatory changes with no evidence of lymphoma. Collectively, for the post-therapy PET: PPV, NPV, Se, Sp were 71.4% (95% CI 30–95%), 79.2% (95% CI 57–92%), 50% (95% CI 20–80%), and 90.4% (95% CI 68–98%), respectively. Conclusions: Our study demonstrated an acceptable NPV and Sp but low PPV and Se for mid- and post- therapy PET in patients with aggressive NHL treated with rituximab. Furthermore, negative mid-therapy PET did not assure continuous response to therapy. Our findings also emphasize the importance of confirmatory biopsies in patients with post-therapy positive PET scans prior to initiation of second line therapy.

Outcomes of Second-Line Chemotherapy and Autologous Stem Cell Transplantation for Primary Refractory Diffuse Large B Cell Lymphoma

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4445-4445
Author(s):  
David Telio ◽  
Clement Ma ◽  
Richard Tsang ◽  
Armand Keating ◽  
Michael Crump ◽  
...  
Keyword(s):  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Primary Treatment ◽  
Salvage Chemotherapy ◽  
High Dose ◽  
Primary Therapy ◽  
Second Line ◽  
High Dose Therapy ◽  
Large B Cell Lymphoma

Abstract Introduction: Patients (pts) with primary refractory Diffuse Large B Cell Lymphoma (REF DLBCL - defined as progession within 3 months of completion of primary therapy) sensitive to salvage chemotherapy are treated with high dose therapy and autologous stem cell transplantation (ASCT). The randomized Parma trial demonstrated survival benefit for patients with chemosensitive relapse undergoing ASCT but did not include primary refractory cases, thus current practice is based largely on retrospective series Methods: We conducted a retrospective review of 112 consecutive cases of REF DLBCL identified from our database between 1999–2007. All pts had evidence of stable or progressive disease (SD or PD) following primary treatment. Responses were assessed retrospectively using International Workshop Criteria (JCO 1999). Logistic regression was used to predict overall response rate (ORR) to salvage therapy; Cox Proportional-Hazards regression was used to analyze overall survival (OS) and progression-free survival (PFS). Salvage chemotherapy consisted of 2–3 cycles of platinum-based therapy; responding pts proceeded to PBSC mobilization and subsequent ASCT. High dose therapy consisted of VP16 60 mg/kg day –4 and melphalan 180 mg/m2 day –3 with PBSC infusion day 0. Pts with bulk disease (³ 5 cm) at progression received involved field radiation post-ASCT. Results: Median age was 46 (range 19–67); 77% had ECOG of 0–1 and 46% had limited stage disease at primary treatment failure. Where available (n=77), LDH was elevated in 74%. 21% had &gt; 1 extranodal site. Primary treatment consisted of: CHOP 66%, R-CHOP 33% or ABVD 1%; radiotherapy was given in 15 pts. Response to primary therapy was: CR 9%, PR 31%, SD 20% and PD 41%. Second-line chemotherapy consisted of: DHAP 49, ESHAP 31, GDP (gemcitabine, dexamethasone, cisplatin) 24, or another platinum based-regimen 8. 5 pts received rituximab with the salvage regimen. ORR to first salvage chemotherapy was 24%. 2/35 pts receiving a second line and 0/6 pts receiving a third line of non-cross-resistant salvage therapy achieved response. 28 pts (25%) underwent ASCT. 6 pts received post-ASCT radiation as consolidation. With a median follow-up of 5.9 months (range 0.9–93.8), the median PFS and OS from primary treatment failure were 3 and 10 months respectively. OS may have been overestimated due to a high rate of loss to follow up after progression and subsequent censoring. In pts who underwent ASCT (median follow-up 18 months, range 0.3–89 months), median PFS was15 months after ASCT while median OS was not reached. ORR to salvage chemotherapy was predicted by normal LDH (OR=3.1; 95% CI=1.0–9.1; p=0.04). Proceeding to ASCT was predicted by normal LDH (OR=4.3; 95% CI=1.5–12.5; p=0.007), ECOG 0–1 (OR=5.2; 95% CI=1.1–23.6; p=0.03), and CR/PR with primary treatment (OR=3.2; 95% CI=1.5–12.3; p=0.01). Inferior PFS was found in pts with elevated LDH (HR=2.5; 95% CI=1.3–4.6; p=0.004), ECOG ≥ 2 (HR=1.8; 95% CI=1.1–2.9; p=0.01), and in pts having SD/PD with primary treatment (HR=1.7; 95% CI=1.1–2.6; p=0.02). OS was reduced in pts with elevated LDH (HR=5.3; 95% CI=1.8–15.0; p=0.002) and ECOG ≥ 2 (HR=2.7; 95% CI=1.4–5.2; p=0.004). Age, stage, number of extranodal sites and prior rituximab treatment were not significant predictors of any outcome. Conclusions: In summary, outcomes in patients with REF DLBCL are poor with an ORR of 25% to salvage chemotherapy and a median PFS of 15 months post-ASCT. Elevated LDH and poor functional status predict for inferior overall survival. Novel treatment approaches should be pursued in REF DLBCL.

Outcomes of Nodular Lymphocyte Predominant Hodgkin's Lymphoma (NLPHL) Patients Treated with R-CHOP.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2812-2812 ◽  
Author(s):  
Michelle A. Fanale ◽  
Chao-Ming Lai ◽  
Peter McLaughlin ◽  
Jorge Romaguera ◽  
Luis Fayad ◽  
...  
Keyword(s):  
B Cell ◽  
Research Funding ◽  
Hodgkin’S Lymphoma ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Stage I ◽  
Hodgkin's Lymphoma ◽  
Stage Iii ◽  
Field Radiation

Abstract Abstract 2812 Introduction: Nodular lymphocyte predominant Hodgkin's lymphoma (NLPHL) constitutes 5% of Hodgkin's lymphoma (HL) diagnoses. Recently gene expression profiling has shown significant overlap between NLPHL, T-cell-rich B cell lymphoma (TCRBCL), and classical HL (Brune, V et al, J Exp Med, 2008). NLPHL patients also have an approximate 7% risk of transformation at 10 years to diffuse large B-cell lymphoma (DLBCL) and TCRBCL (Al-Mansour, M et al, JCO, 2010). Data from multiple groups (Nogova, L et al, Ann Onc, 2005, Chen, RC et al, JCO, 2010, Wirth, A et al, Cancer, 2005) support extended progression-free survivals (PFS) for stage IA/IIA patients treated with radiation alone. While chemotherapy is generally recommended for patients with stage IB/IIB or III/IV disease, there is lack of guidelines on whether classical HL-directed regimens, such as ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine), or B-cell lymphoma-directed regimens, such as R-CHOP (rituximab, cychlophosphamide, doxorubicin, vincristine, prednisone) should be used. Given the similarities between NLPHL and indolent CD20+ B-cell non-Hodgkin's lymphoma (NHL), our group started using the R-CHOP regimen for patients with NLPHL requiring systemic therapy. In order to examine the potential efficacy of this approach, we conducted a retrospective analysis of treatment outcomes in patients who received R-CHOP versus other regimens treated at UT MDACC from 1995 to 2010. Results: 83 patients were referred. 6 patients were found to have NLPHL with transformation to DLBCL or TCRBCL. 3 had alternative diagnoses. 11 lacked full immunophenotyping to confirm diagnosis. 63 patients had confirmed diagnoses of NLPHL (39 stage I/II and 24 stage III/IV). 52 NLPHL patients were evaluable (10 did not complete full treatment planning or were lost to follow-up and 1 is currently completing therapy). 7 patients had extranodal disease (thyroid, breast, lung, liver, bone marrow/cortex) and 8 had spleen involvement. Overall their median age at diagnosis was 40, male:female ratio was 2.5, and median follow-up is 46 months (range 8–149 months). 6 patients had relapse of NLPHL, 2 patients had transformation at a median of 39 months (1 to DLBCL, 1 to TCRBCL), 4 patients died (1 from acute myelogenous leukemia with deletion 7, 1 from DLBCL, 2 from unrelated causes while in remission), and 2 patients underwent autologous stem cell transplant (1 for relapsed NLPHL in 3rd complete remission and 1 for transformation to TCRBCL). Therapies for stage I/II NLPHL included: surgical excision alone (2 patients with stage IA disease declined radiation treatment), subtotal nodal irradiation (STNI), mantle field radiation, involved field radiation (IFRT), rituximab (R) alone and plus IFRT, ABVD plus STNI, R-ABVD, COPP (cyclophosphamide, vincristine, procarbazine, prednisone) plus IFRT, and R-CHOP alone and plus IFRT. Therapies for stage III/IV included: mantle field radiation (1 patient who declined chemotherapy), NOVP (mitoxantrone, vincristine, vinblastine, prednisone) plus mantle field radiation, ABVD, R-ABVD, R-CHOP alone and plus IFRT. A total of 15 patients received R-CHOP alone (4 stage I/II, 11 stage III/IV) and 5 patients received R-CHOP plus IFRT (4 stage I/II, 1 stage III/IV). Response to R-CHOP as assessed by CT scan criteria was 100% overall response rate (ORR) with 90% complete remissions (CR). No R-CHOP patients have had relapses or transformation with a median follow-up of 42 months (range 8–111 months). One patient treated with R-CHOP died of unrelated causes while in remission. However, with other therapies 19% have relapsed after median remissions of 38 months (range 4 to 72 months). R-CHOP when compared to other treatments has a trend towards improved PFS (Figures 1, 2, and 3). Survival rates for NLPHL patients at 5 years with 95% confidence intervals are: R-CHOP: PFS 0.95 (0.86, 1), OS (overall survival) 0.95 (0.86, 1) and other therapies: PFS 0.71 (0.55, 0.92), OS 0.91 (0.8, 1). Conclusions: Our data demonstrates that RCHOP is an effective regimen for the treatment of patients with NLPHL. A prospective evaluation of R-CHOP as a front-line treatment of NLPHL is under consideration. Disclosures: Fanale: Seattle Genetics: Research Funding; Novartis: Honoraria, Research Funding; Millenium: Research Funding; Genentech: Research Funding. Off Label Use: Given the CD20 positivity of nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) rituximab has been evaluated previously for relapsed NLPHL and was shown to be efficacious. Rituximab however is not FDA approved for NLPHL. This is a retrospective study that evaluates the use of R-CHOP and other therapies for NLPHL. Current NCCN guidelines support consideration of R-CHOP for NLPHL treatment, and given the rarity of the disease there is no one defined preferred chemotherapy regimen. This information will be disclosed to the audience. Fayad:Genentech: Research Funding. Rodriguez:Genentech: Research Funding. Shah:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Millenium: Research Funding; Novartis: Research Funding. Younes:Genentech: Honoraria, Research Funding; SBIO: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Seattle Genetics: Honoraria, Research Funding.

Efficacy and Safety of Reduced Dose Intensity R-CHOP in Elderly Patients with Diffuse Large B Cell Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 3674-3674
Author(s):  
Jungmin Jo ◽  
Dok Hyun Yoon ◽  
Sang-wook Lee ◽  
Chan-Sik Park ◽  
Jooryung Huh ◽  
...  
Keyword(s):  
Febrile Neutropenia ◽  
Elderly Patients ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Efficacy And Safety ◽  
Chop Chemotherapy ◽  
Reduced Dose ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Abstract Abstract 3674 Introduction Chemotherapy with curative intent should be given to all patients with diffuse large B-cell lymphoma (DLBCL), however, elderly patients often have a variety of co-morbidities and poor functional status resulting in high rate of adverse events related to treatment such as anthracycline-related cardiotoxicity or hematologic toxicities. Although primary prophylactic granulocyte colony-stimulating factor (G-CSF) is often used to prevent severe neutropenia, pharmaco-economic arguments exist and it is not available for considerable populations worldwide. Therefore, we aimed to assess the efficacy and safety of the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone with rituximab (R-CHOP) with reduced doses of cyclophosphamide and doxorubicin by 25% in elderly patients with DLBCL. Patients and methods Medical records of a total of 118 patients aged ≥65 years with DLBCL, newly diagnosed between September 2007 and March 2012, were retrieved from the database. All patients received R-CHOP chemotherapy every 3 weeks with reduced doses of cyclophosphamide (562.5 mg/m2) and doxorubicin (37.5 mg/m2). No patient received primary prophylactic G-CSF, however, it was allowed to those who suffered from febrile neutropenia or grade 4 neutropenia (ANC<500/μl) during treatment. Doses of cyclophosphamide and doxorubicin were reduced by additional 25% in those patients. Results The median age was 72 years (range 65–85) at diagnosis and the cohort included 9 (7.6%) very elderly patients (≥80 years). The Ann Arbor stage was stage I or II in 43 patients (36.4%) and III or IV in 75 (63.6%). The international prognostic index (IPI) scores were 0–1 in 31 patients (26.3%), 2 in 21 (17.8%), 3 in 25 (21.2%), and 4–5 in 41 (34.8%). Performance status was good (ECOG <2) in all the patients. The median number of cycle was 6 (range 1–8). Eighty-seven patients (73.7%) completed the planned cycles of chemotherapy. Thirty-one patients failed to finish chemotherapy owing to intolerance to treatment (35.5%), infection (12.9%), other toxicities (25.8%), or follow-up loss (25.8%). The overall response rate (ORR) was 78% with a complete response (CR) rate of 65.3%. With a median follow-up duration of 22.9 months (range 4.5–58.7), 2-year progression-free survival (PFS) and overall survival (OS) were 60.6% and 68.7% respectively. Grade 3/4 neutropenia and thrombocytopenia were observed in 55 (46.6%) and 12 patients (10.2%), respectively. Thirty-two patients (27.1%) experienced febrile neutropenia and 41 patients (34.7%) required additional dose reduction. Six patients (5.1%) suffered from life-threatening toxicities and eventually died. Conclusions The R-CHOP chemotherapy with reduced dose of cyclophosphamide and doxorubicin doesn't seem to attenuate the efficacy of R-CHOP chemotherapy in the elderly patients when compared with the original report (Coiffier et al, NEJM 2002). However, toxicities still matter despite upfront dose reduction. Tailored strategies or other regimens with better toxicity profiles are in need for these patients. Disclosures: No relevant conflicts of interest to declare.

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