Challenges and Opportunities in the Management of Diffuse Large B Cell Lymphoma in Older Patients

Abstract Abstract 2693 Introduction: Treatment of Diffuse Large B-Cell Lymphoma (B-DLCL) is not well coded in the elderly patients. They may receive full dose immunochemotherapy, low dose chemotherapy or palliative treatment regarding co morbidities, Performans Status (PS), psychological, social or mental state. The lack of age-adapted prognosis factors including geriatric scales induce a subjective choice for the treatment. The purpose of the study is to evaluate the outcome of all the patients treated in a single institute for a B-DLCL, with comparison of age of diagnosis and treatment received. Methods: All patients with B-DLCL, age≥70 years, treated in the Paoli-Calmettes institute between 1995 and 2008 were included, excepted patients with intra-ocular and cerebral localizations or with a “Burkitt-like” histology. Were also excluded patients with incomplete data. Treatments were simplified for statistic analysis in three types: CHOP Like (CH-L): three chemotherapies with anthracyclin (or etoposide in place if cardiac impossibility) with conventional doses, mini-CHOP-Like (mCH-L): with reduce doses of anthracyclin and cyclophosphamide, or COP Like (C-L): two agents without anthracyclin. Factors studied in the different items are systematically Age (70–79 vs olders), PS (0–1 vs 2–4), LDH, Ann Arbor stage (AA:1–2 vs 3–4) and type of chemotherapy. Results: From 1995 to 2008, 212 patients with B-DLCL were admitted in the Paoli-Calmettes institute for a B-DLCL. The median age was 76 years [range 70–90], 70% of the patients had a PS=0–1 and 30% a PS=2–4, LDH was increased in 55% of patients, AA was 3–4 in 58% of cases. The repartition of chemotherapy was 56% for CH-L, 33% for mCH-L and 11% for C-L. In the 70–79 age subgroup, CH-L is predominant (67% vs 25% for the older patients, p<0.0001). Four patients died before therapy initiation. Survival curves for mCH-L and C-L are identical, with no difference of population characteristics and patients are grouped for the final analysis (mCH-CL group). Rituximab was added to the chemotherapy in 63% of cases. Overall Survival at 12 and 60 month was respectively 73% and 47% with a median [IC95] of 48.8 month. Age at diagnosis is statistically significant with a 5-year survival of 53% and 29% for respectively 70–79 years and older (p=0.0045). Patients characteristics of the age subgroups are different only for the type of chemotherapy infused (p<0.0001) and not for the others factors analyzed. Choice of chemotherapy was also important (P=0.0011) with an OS of 55% and 37% respectively for CH-L and mCH-CL protocols. In this case, patients characteristics are different in term of date of diagnosis (p<0.001), age of diagnosis (p<0.001), PS (0.04) and AA (0.011). Surprisingly, there is no difference in OS when rituximab was given (p=0.7), and despite the difference of treatment, there is no difference of incidence of relapse in the two age groups (p=0.97). Conclusion: Survival of our elderly population of patients with B-DLCL is comparable to the literature. With non-selected patients, repartition of factors from the IPI score is not different in the two age subgroups, but the more intensive chemotherapy is given in the less older patients. Moreover, OS is increased in this CH-L protocol, in contrast with the same incidence of relapse. Furthermore, the use of rituximab, a major treatment of B-DLCL in the elderly, do not influence OS in this non-selected population of patients. These data confirm the requirement of a more discriminant prognosis model than the IPI score for the daily practice, including relevant geriatric factors. Disclosures: No relevant conflicts of interest to declare.

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High-Grade Diffuse Large B-Cell Lymphoma in Elderly Patients: Russian Multicenter Trial Results in R-EPOCH/R-HMA Protocol

Blood ◽

10.1182/blood.v128.22.5386.5386 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5386-5386

Author(s):

Olga A. Gavrilina ◽

Eugene E. Zvonkov ◽

Elena N. Parovichnikova ◽

Nelly G. Gabeeva ◽

Vera V. Troitskaya ◽

...

Keyword(s):

Bone Marrow ◽

Elderly Patients ◽

B Cell ◽

Older Patients ◽

Cell Lymphoma ◽

Bone Marrow Involvement ◽

B Cell Lymphoma ◽

High Grade ◽

Large B Cell Lymphoma ◽

Large B Cell

Abstract Background: The number of elderly patients with diffuse large B-cell lymphoma (DLBCL) in our aging society continues to rise. Median of age for patients with diffuse large B-cell lymphoma (DLBCL) is 60. Approximately 50% of older patients with DLBCL are defined as high-grade by IPI and these forms are characterized by aggressive course and poor response to standard chemotherapy (CT). Intensive protocols cannot be performed due to their toxicity for older patients with comorbidity. Addition of R-HMA to R-DA-EPOCH favourably changes the outcome in patients with untreated high-grade diffuse large B-cell lymphoma and didn't have higher toxicity [ASH 2015 # 2708]. Aim: To evaluate the efficacy and toxicity of R-EPOCH/R-HMA protocol in older patients with untreated high-grade diffuse large B-cell lymphoma. Patients and Methods: 19 untreated older DLBCL patients from 4 centers were enrolled in a prospective study between August 2013 - July 2016; stage II-IV; ECOG 0-3; median age 66 years (60-78); age ≥70y/60<70y 21%/79%; M/F 52%/48%; IPI: 52% high-intermediate and 48% high risk; 26% with bone marrow involvement. Severe comorbidity was diagnosed in 8 (42%) patients (coronary heart disease, hypertonic disease, chronic obstructive pulmonary disease and arrhythmia). All patients underwent 4-6 courses (2-3 cycles) of chemotherapy: R-EPOCH (standard dose and scheme), R-HMA (R 375 mg/m2 d1, MTX 500 mg/m2 24 hours d 2, AraC 1000 mg/m2 q 12 hrs d 3-4). In 3 cases of DLBCL with bone marrow involvement BEAM conditioning and autologous stem cell transplantation were applied. Results: The median follow-up is 18 months (3-37). There was no mortality associated with toxicity. The main non-hematological toxicities of R-HMA were infections (mucositis, pneumonia, sepsis, enteropathy) grades 1-2 and 3-4 in 90% and 10%, respectively. Hematological toxicity grade 4 for less than 4 days we observed only after courses R-HMA. Complete remission (CR) was achieved in 18 (100%) patients and 1 patient in the treatment now. There are four failures in patients older than 60 years: three relapses (after 6 and two after 14 month CR) and one death after 7 month CR by reasons not related with DLBCL. With a median follow 18 months overall and event-free survival of 19 older patients constituted 93,8% and 75,9%, respectively (Fig.1). There is no difference in older patients according to stage, IPI, LDH level, ECOG status for OS and EFS. So the combination of R-EPOCH/R-HMA may be considered as optimal intensive approach in older patients. Conclusions: TheR-EPOCH/R-HMA protocol demonstrated acceptable toxicity and high efficacy in older patients with high-grade DLBCL. Figure 1 Overall (A) and Event-free (B) survival in elderly patients with DLBCL. Figure 1. Overall (A) and Event-free (B) survival in elderly patients with DLBCL. Disclosures No relevant conflicts of interest to declare.

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Chemo-immunotherapy dosing in older patients with diffuse large B-cell lymphoma: is this how we should treat our parents?

Leukemia & Lymphoma ◽

10.3109/10428194.2012.672737 ◽

2012 ◽

Vol 53 (8) ◽

pp. 1435-1436 ◽

Cited By ~ 2

Author(s):

Brian K. Link

Keyword(s):

B Cell ◽

Older Patients ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Large B Cell Lymphoma ◽

Large B Cell

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Improved survival with rituximab-based chemoimmunotherapy in older patients with extranodal diffuse large B-cell lymphoma

Leukemia Research ◽

10.1016/j.leukres.2014.04.009 ◽

2014 ◽

Vol 38 (8) ◽

pp. 866-873 ◽

Cited By ~ 10

Author(s):

Adam J. Olszewski ◽

Eric S. Winer ◽

Jorge J. Castillo

Keyword(s):

B Cell ◽

Older Patients ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Large B Cell Lymphoma ◽

Large B Cell

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A phase II trial of bendamustine in combination with rituximab in older patients with previously untreated diffuse large B-cell lymphoma

British Journal of Haematology ◽

10.1111/bjh.14232 ◽

2016 ◽

Vol 175 (2) ◽

pp. 281-289 ◽

Cited By ~ 32

Author(s):

Steven I. Park ◽

Natalie S. Grover ◽

Oludamilola Olajide ◽

Adam S. Asch ◽

James G. Wall ◽

...

Keyword(s):

B Cell ◽

Phase Ii ◽

Older Patients ◽

Phase Ii Trial ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Large B Cell Lymphoma ◽

Large B Cell

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Association of the Geriatric 8 with treatment intensity and prognosis in older patients with diffuse large B‐cell lymphoma

British Journal of Haematology ◽

10.1111/bjh.17554 ◽

2021 ◽

Author(s):

Shin Lee ◽

Kei Fujita ◽

Tetsuji Morishita ◽

Kana Oiwa ◽

Hikaru Tsukasaki ◽

...

Keyword(s):

B Cell ◽

Older Patients ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Treatment Intensity ◽

Large B Cell Lymphoma ◽

Large B Cell

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Characterizing Autoimmune Disease-Associated Diffuse Large B Cell Lymphoma in a SEER-Medicare Cohort

Blood ◽

10.1182/blood.v128.22.4214.4214 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4214-4214

Author(s):

Jean L. Koff ◽

Ashish Rai ◽

Christopher Flowers

Keyword(s):

Risk Factors ◽

Autoimmune Disease ◽

B Cell ◽

Older Patients ◽

Research Funding ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Large B Cell Lymphoma ◽

Large B Cell ◽

Related Survival

Abstract Introduction: Severe immune dysregulation as seen in human immunodeficiency virus infection, immunosuppression after solid organ transplant, and autoimmune (AI) disease is known to act as a major risk factor for non-Hodgkin lymphoma (NHL). Recently, the InterLymph Subtypes Project pooled cases and controls to provide well-powered comparisons of risk factors for specific NHL subtypes, such as diffuse large B cell lymphoma (DLBCL), and showed that B cell-activating AI diseases in general (odds ratio 2.4; 95% confidence interval 1.8-3.1) and systemic lupus erythematosus (SLE) and Sjögren's syndrome (SS) in particular were strongly associated with increased DLBCL risk after controlling for all other risk factors (Cerhan J Natl Cancer Inst Monogr. 2014). However, little is known about the demographics or clinical outcomes of DLBCL that arises in the setting of AI disease. We examined the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database to determine the frequency of common B cell AI diseases among older patients with DLBCL and characterize the patterns of presentation, treatment, and survival for DLBCL patients with concomitant AI disease. Methods: We used the SEER database for patients diagnosed 2002-2009 linked to their Medicare claims data through 2011 to characterize presentation, treatment, and survival patterns in patients with DLBCL, including those with rheumatoid arthritis (RA), SLE, SS, and other B cell-mediated autoimmune diseases as defined by InterLymph criteria (autoimmune hemolytic anemia, Hashimoto's thyroiditis/hypothyroidism, myasthenia gravis; pernicious anemia; Wang Am J Epidemiol. 2015). Patient age, sex, race/ethnicity, region of residence, marital status, year of diagnosis, cause of death, census tract-level characteristics (education, poverty, and metropolitan/urban/rural status), stage, B symptoms, and nodal or extranodal primary site of involvement were identified from the SEER data. Assessments of poor performance status, anemia, the Charlson comorbidity index, survival, and treatment strategies were identified using Medicare inpatient, outpatient and physician claims. Treatments were categorized as: rituximab (R), cyclophosphamide and vincristine (CVP), R-CVP; cyclophosphamide, hydroxydaunorubicin, and vincristine (CHOP), and R-CHOP. Patients who did not receive any DLBCL-directed treatment within 6 months of diagnosis were categorized separately. We examined the baseline clinical characteristics for patients with DLBCL and RA, SLE, SS, or any B cell-mediated autoimmune disease, plotted overall survival and lymphoma-related survival for these groups and compared median survival times. Results: Patient characteristics are summarized in the Table. With the exception that patients with DLBCL and AI disease were more commonly female[KJL1] [CF2] , patients with DLBCL and RA, SLE, SS, or other B cell AI diseases have similar baseline presenting features as other DLBCL patients and received similar first line treatments. There was a trend towards decreased lymphoma-related survival in patients with SLE and DLBCL compared to all other groups, but this difference was not statistically significant in this cohort (Figure) [KJL3] [KJL4] . Conclusions: In this retrospective claims-based cohort of older patients with DLBCL, concomitant AI disease was uncommon and was more likely to occur in female DLBCL patients, which likely reflects the higher incidence of AI disease in women. The possibility of lower lymphoma-related survival for these patients should be explored in future studies. Disclosures Flowers: Millenium/Takeda: Research Funding; NIH: Research Funding; TG Therapeutics: Research Funding; Pharmacyclics, LLC, an AbbVie Company: Research Funding; Mayo Clinic: Research Funding; Infinity: Research Funding; ECOG: Research Funding; Acerta: Research Funding; AbbVie: Research Funding; Roche: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Gilead: Consultancy, Research Funding.

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