R‐COMP versus R‐CHOP as first‐line therapy for diffuse large B‐cell lymphoma in patients ≥60 years: Results of a randomized phase 2 study from the Spanish GELTAMO group

Abstract

The use of non‐pegylated liposomal doxorubicin (Myocet®) in diffuse large B‐cell lymphoma (DLBCL) has been investigated in retrospective and single‐arm prospective studies. This was a prospective phase 2 trial of DLBCL patients ≥60 years old with left ventricular ejection fraction (LVEF) ≥55% randomized to standard R‐CHOP or investigational R‐COMP (with Myocet® instead of conventional doxorubicin). The primary end point was to evaluate the differences in subclinical cardiotoxicity, defined as decrease in LVEF to <55% at the end of treatment. Secondary objectives were efficacy, safety, and variations of troponin and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) and LVEF along follow‐up. Ninety patients were included, 45 in each group. No differences were observed in the percentage of patients with LVEF <55% at end of treatment (11% in R‐CHOP arm vs. 7% in R‐COMP arm, p = 0.697) or at 4 months (10% vs. 6%, respectively, p = 0.667) and 12 months (8% vs. 7%, respectively, p = 1). However, a higher percentage of R‐CHOP compared with R‐COMP patients showed increased troponin levels in cycle 6 (100% vs. 63%, p = 0.001) and at 1 month after treatment (88% vs. 56%, respectively, p = 0.015). Cardiovascular adverse events were seen in five R‐CHOP patients (nine episodes, four grade ≥3) and in four R‐COMP patients (five episodes, all grade 1–2). No significant differences in efficacy were observed. In conclusion, R‐COMP is a feasible immunochemotherapy schedule for DLBCL patients ≥60 years, with similar efficacy to R‐CHOP. However, the use of non‐pegylated doxorubicin instead of conventional doxorubicin was not associated with less early cardiotoxicity, although some reduced cardiac safety signals were observed. Trial registration: ClinicalTrials.gov Identifier: NCT02012088.

Targeted Drug Delivery and Theranostic Strategies in Malignant Lymphomas

“…Importantly, in a large meta-analysis of patients with DLBCL treated with NPLD, Visco et al endorsed the value of NPLD both in terms of response and survival [80]. In contrast, although Sancho et al confirmed the noninferiority of NPLD to conventional doxorubicin as part of frontline immunochemotherapy in patients with so far untreated aggressive lymphomas, the substitution with NPLD was not associated with less early cardiotoxicity, although some reduced cardiac safety signals were observed [81]. Similarly, NPLD did not reduce cardiotoxicity, although cardiac safety signals were elevated in R-CHOP compared to R-COMP in an Austrian randomized phase III study [82].…”

R-CEOP as first-line treatment for anthracycline-ineligible patients with diffuse large B-cell lymphoma

“…There are several other potential treatment options for newly diagnosed DLBCL patients with a contraindication for doxorubicin. Non-pegylated liposomal doxorubicin has been assessed in patients diagnosed with DLBCL, with no difference observed in cardiotoxicity [7,8]. In combination with rituximab, anthracyclinefree regimens include cyclophosphamide, vincristine and prednisone (R-COP), gemcitabine and oxaliplatin (R-GemOx), lenalidomide (R2), bendamustine, gemcitabine, cyclophosphamide, vincristine, and prednisolone (R-GCVP) [9][10][11][12].…”

Oncological Treatment-Related Fatigue in Oncogeriatrics: A Scoping Review

“…In fact, no data regarding fatigue are available in papers reporting the CHOP regimen [267], even when dedicated to older patients [280][281][282]. All but one trial specifically dedicated to older patients receiving R-CHOP-based regimens did not provide data regarding fatigue [283]; one study on patients aged ≥60 years reported 49% any-grade fatigue and 0% grade 3 or more fatigue with the R-CHOP regimen [284]. Considering other chemotherapy regimens, the frequency of any-grade fatigue was moderate-to-high but with relatively low levels of grade 3 or more fatigue, with the exception of R-DHAP (9%) and R-COMP in older patients (7%) [284].…”

“…All but one trial specifically dedicated to older patients receiving R-CHOP-based regimens did not provide data regarding fatigue [283]; one study on patients aged ≥60 years reported 49% any-grade fatigue and 0% grade 3 or more fatigue with the R-CHOP regimen [284]. Considering other chemotherapy regimens, the frequency of any-grade fatigue was moderate-to-high but with relatively low levels of grade 3 or more fatigue, with the exception of R-DHAP (9%) and R-COMP in older patients (7%) [284]. R-CVP was associated with moderate any-grade fatigue rates (53%) and almost no grade 3 or more fatigue (<1%) in the overall population but much more frequent grade 3 or more fatigue in the older patients (47 %) [285], calling into question its use in this specific population.…”

“…Diffuse large B-cell lymphoma CHOP-21 [286] CHOP: data specific to older patients (60-80) [280][281][282] nr nr nr nr DHAP [287] nr nr ESHAP [288][289][290] nr nr CNOP [286] nr nr ACOD [291] 3 0 Fludarabine/mitoxantrone [292] nr nr R-CHOP-21 [277,278] 27-46 3 R-CHOP: data specific to older patients (>60) [280][281][282]284,293,294] 49 0 R-CHOP-Lenalinomide maintenance: data specific to older patients (58-80) [295] nr nr R-miniCHOP regimen specific to older patients (≥80) [283] nr nr R-COMP [284,296]: data specific to older patients 53 7 R-mini-CHP: regimen specific to older patients (≥80) [297] nr nr R-mini-CEOP regimen specific to "frail" patients (64-84 years) [298] nr nr R-CVP [277] 53 <1 R-mini-CVP regimen specific to older patients (≥80) [285] 58 47 DA-EPOCH-R [299] nr nr R-pola-CHP 21 [278] 26 1 R-DHAP [279] nr 9 R-GemOx [300] nr nr Lenalinomide-rituximab [301][302][303] nr 13-23 Lenalinomide [302][303][304] 34 7-9 Tafasitamab-lenalidomide (L-MIND) [305] 15 2 CAR-T Lisocabtagene maraleucel (TRANSCEND NHL 001) [306] 44 1 CAR-T Axicabtagene ciloleucel (ZUMA-1) [307] 51 2...…”