Combination of ofatumumab and reduced-dose CHOP for diffuse large B-cell lymphomas in patients aged 80 years or older: an open-label, multicentre, single-arm, phase 2 trial from the LYSA group

Peyrade, Fréd́eric; Bologna, Serge; Delwail, Vincent; Emile, Jean François; Pascal, Laurent; Fermé, Christophe; Schiano, Jean‐Marc; Coiffier, Bertrand; Corront, Bernadette; Farhat, H.; Fruchart, Christophe; Ghesquières, Hervé; Macro, Margaret; Tilly, Hervé; Choufi, Bachra; Delarue, Richard; Fitoussi, Olivier; Gabarre, Jean; Haı̈oun, Corinne; Jardin, Fabrice

doi:10.1016/s2352-3026(16)30171-5

Cited by 93 publications

(88 citation statements)

References 23 publications

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“…As such, prospective evidence in patients ≥80 years is limited to two phase II trials. These trials show that patients ≥80 years receiving attenuated or 'mini' CHOP (25 mg m À2 doxorubicin; 400 mg m À2 cyclophosphamide, 1 mg vincristine) with an anti-CD20 monoclonal antibody can induce a sustained remission in 50-60% [7,8]. These studies support the use of modified anthracycline-based therapy in patients ≥80 years.…”

Section: Introductionmentioning

confidence: 70%

Impact of intended and relative dose intensity of R‐CHOP in a large, consecutive cohort of elderly diffuse large B‐cell lymphoma patients treated with curative intent: no difference in cumulative incidence of relapse comparing patients by age

et al. 2019

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Background The increasing incidence of diffuse large B‐cell lymphoma (DLBCL) in ageing populations places a significant burden on healthcare systems. Co‐morbidity, frailty, and reduced organ and physiological reserve contribute to treatment‐related complications. The optimal dose intensity of R‐CHOP to optimize outcome across different ages with variable frailty and comorbidity burden is unclear. Objectives and Methods We examined the influence of intended (IDI) and relative (RDI) dose intensity of the combination of cyclophosphamide and doxorubicin, age and comorbidity on outcomes for DLBCL patients ≥70 years in a representative, consecutive cohort across eight UK centres (2009–2018). We determined predictors of survival using multivariable Cox regression, and predictors of recurrence before death using competing risks regression. Results Porgression‐free survival (PFS) and overall survival (OS) were significantly inferior in patients ≥80 vs. 70–79 years (P < 0.001). In contrast, 2‐year cumulative relapse incidence, when accounting for non‐relapse mortality as a competing risk, was no different between 70–79 vs. ≥80 years (P = 0.27) or comorbidity status (CIRS‐G: 0–6 vs. >6) (P = 0.27). In 70–79 years, patients with an IDI ≥80% had a significantly improved PFS and OS (P < 0.001) compared to IDI < 80%. Conversely, in patients ≥80 years, there was no difference in PFS (P = 0.88) or OS (P = 0.75) according to IDI <80% vs. ≥80%. On multivariable analysis, when comparing by age, there was a significantly higher cumulative relapse rate for patients aged 70–79 years with an IDI <80% (vs. >80%) (P = 0.04) but not for patients ≥80 years comparing IDI (P = 0.32). Conclusion ‘R‐mini‐CHOP' provides adequate lymphoma‐specific disease control and represents a reasonable treatment option in elderly patients ≥80 years aiming for cure.

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Section: Introductionmentioning

confidence: 70%

Impact of intended and relative dose intensity of R‐CHOP in a large, consecutive cohort of elderly diffuse large B‐cell lymphoma patients treated with curative intent: no difference in cumulative incidence of relapse comparing patients by age

et al. 2019

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“…The GELA non‐Hodgkin lymphoma trial demonstrated that the long‐term survival outcomes were improved for these patients when rituximab was administered together with CHOP therapy, and this result later was confirmed by the RICOVER‐60 trial . Approaches using dose‐reduced CHOP with an anti‐CD20 antibody also demonstrated favorable progression‐free survival with tolerable toxicity in patients aged ≥80 years, but both appear to produce inferior outcomes compared with patients aged 80 years who were treated with R‐CHOP at standard doses on GELA LNH‐98.5 . Comorbidities and changes in functional status might complicate anthracycline‐based chemotherapy, as shown in a large epidemiological study that analyzed treatment patterns for older patients with DLBCL in the United States .…”

Section: Discussionmentioning

confidence: 98%

“…40 Approaches using dose-reduced CHOP with an anti-CD20 antibody also demonstrated favorable progression-free survival with tolerable toxicity in patients aged ≥80 years, but both appear to produce inferior outcomes compared with patients aged 80 years who were treated with R-CHOP at standard doses on GELA LNH-98.5. 41,42 Comorbidities and changes in functional status might complicate anthracycline-based chemotherapy, as shown in a large epidemiological study that analyzed treatment patterns for older patients with DLBCL in the United States. 7 The toxicities related to R-CHOP therapy are exacerbated with increasing age, functional disability, and comorbidity.…”

Section: Discussionmentioning

confidence: 99%

A population‐based multistate model for diffuse large B‐cell lymphoma–specific mortality in older patients

Çaǧlayan

Goldstein

Ayer

et al. 2019

Cancer

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BACKGROUND: Despite effective therapies, outcomes for diffuse large B-cell lymphoma (DLCBL) remain heterogeneous in older individuals due to comorbid diseases and variations in disease biology. METHODS: Using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, the authors conducted a multistate survival analysis of 11,780 patients with DLBCL who were aged ≥65 years at the time of diagnosis (2002–2009). Cox proportional hazards models were used to specify the impact of prognostic factors on overall survival and cause-specific deaths, and the Aalen-Johansen estimator was used to project the course of DLBCL over time with or without standard therapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). RESULTS: Advanced age (hazard ratio [HR] for ages 71–75 years: 1.25; HR for ages 76–80 years: 1.46; HR for ages 81–85 years: 1.88; and HR for age ≥86 years: 2.26), DLBCL stage (HR for Ann Arbor stage II: 1.28; HR for stage III: 1.54; and HR for stage IV: 1.95), Charlson Comorbidity Index (CCI) ≥1 (HR for CCI of 1, 1.15; and HR for CCI >1, 1.37), and not being married (HR, 1.12) were associated with an increased risk of DLBCL-specific death. Being female (HR, 0.91) and of higher socioeconomic status (HR, 0.91) were associated with a lower risk of DLBCL-related mortality after therapy. For patients treated with R-CHOP (3610 patients), the risk of death due to DLBCL was 14.0% and 18.6%, respectively, at 2 and 5 years of treatment and plateaued afterward, confirming a 5-year “cure” point while receiving R-CHOP among older patients. CONCLUSIONS: Conducting a survival analysis over a large data set, the current study evaluated competing risks for death within a multistate modeling framework, and identified age, sex, and CCI as risk factors for DLBCL-specific and other causes of death.

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“…Prephase treatment with corticosteroids +/− vincristine has been utilized in older, frailer, and poor performance status patients, in an effort to optimize tolerability of subsequent more robust regimens [44,45]. Dose-attenuated R-CHOP regimens, as R-miniCHOP or four cycles of induction R-CHOP followed by rituximab consolidation, have been used with clinical success and tolerability in older DLBCL patients [46][47][48][49]. Completion of full-dose intensity anthracycline therapy is often not possible in older patients [50].…”

Section: Discussionmentioning

confidence: 99%

Treatment approaches for older and oldest patients with diffuse large B-cell lymphoma – Use of non-R-CHOP alternative therapies and impact of comorbidities on treatment choices and outcome: A Humedica database retrospective cohort analysis, 2007–2015

Morrison

Hamilton²,

Ogbonnaya³

et al. 2020

Journal of Geriatric Oncology

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a b s t r a c tIntroduction: We characterized real-world treatment patterns in older (65-74 years) and oldest (75-85 years) patients with diffuse large B-cell lymphoma (DLBCL) receiving initial therapy (R-CHOP, non-R-CHOP regimens). Impact of comorbidities on treatment choice, and overall and progression-free survival (OS, PFS) were assessed by age. Patients and Methods: Using the Humedica database, we identified 1436 newly diagnosed patients with DLBCL who received frontline therapy from 1/07-9/15. The 885 patients ≥65 years of age were further evaluated for baseline demographics, comorbidities, initial therapy, and PFS/OS. Results: Of 885 patients, 406 (45.9%) were age 65-74, and 479 (54.1%) age 75-85, years. First line therapy was R-CHOP (61.8%) or non-R-CHOP (38.2%). Although Charlson Comorbidity Index (CCI) scores were similar at baseline, congestive heart failure and myocardial infarction were more common in those receiving non-R-CHOP regimens. Survival outcomes were superior for those receiving initial R-CHOP, versus non-R-CHOP, therapy (median PFS 53.9 versus 27.8 months; two-year PFS 71.2% versus 51.6%, p b .0001; median OS not reached versus 45 months; two-year OS 81.3% versus 62.9%, p b .0001, respectively). Only 10.4% (R-CHOP) and 12.1% (non-R-CHOP) of patients received second line therapies. Two-year OS by age (65-74, 75-85 years) was 66.4% and 39.1%, respectively with R-CHOP (p = .0045), and 74.3% and 54.5%, respectively with non-R-CHOP (p = .004), therapy. Age ≥ 75 years and CCI of 2+ were associated with shorter OS and PFS. Conclusions: This study identified real-world first line treatment patterns for older patients with DLBCL. Our findings support the feasibility of administering standard R-CHOP therapy, even to oldest patients with DLBCL.

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Combination of ofatumumab and reduced-dose CHOP for diffuse large B-cell lymphomas in patients aged 80 years or older: an open-label, multicentre, single-arm, phase 2 trial from the LYSA group

Cited by 93 publications

References 23 publications

Impact of intended and relative dose intensity of R‐CHOP in a large, consecutive cohort of elderly diffuse large B‐cell lymphoma patients treated with curative intent: no difference in cumulative incidence of relapse comparing patients by age

Impact of intended and relative dose intensity of R‐CHOP in a large, consecutive cohort of elderly diffuse large B‐cell lymphoma patients treated with curative intent: no difference in cumulative incidence of relapse comparing patients by age

A population‐based multistate model for diffuse large B‐cell lymphoma–specific mortality in older patients

Treatment approaches for older and oldest patients with diffuse large B-cell lymphoma – Use of non-R-CHOP alternative therapies and impact of comorbidities on treatment choices and outcome: A Humedica database retrospective cohort analysis, 2007–2015

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