R-ceop Regimen

[Coleman John]

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Anthracycline-based chemoimmunotherapy with R-CHOP is the standard treatment for diffuse large B-cell lymphoma (DLBCL) but is associated with increased risks of cardiotoxicity. The alternative regimen R-CEOP substitutes etoposide for doxorubicin and is commonly administered to DLBCL patients with cardiovascular comorbidities, although there is limited evidence supporting its use. This multicenter real-world study included 138 consecutive patients with newly-diagnosed DLBCL treated with R-CEOP and 414 patients treated with R-CHOP matched 1:3 for age and International Prognostic Index. With median follow-up time 4.6 years, R-CEOP was associated with significantly inferior 4-year progression-free survival (32 vs. 52%, p < 0.0001), overall survival (39 vs. 59%, p < 0.0001), and disease-specific survival (48 vs. 69%, p < 0.0001) compared to R-CHOP. R-CHOP should remain the preferred regimen for most patients with DLBCL. While R-CEOP may be a reasonable choice for patients strictly ineligible for anthracyclines, the inferior outcomes of this regimen suggest that this high-risk population requires novel therapeutic approaches.

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Note: This was recommended in NHL-B1 and NHL-B2 "to improve the performance status of patients and to ameliorate side-effects of the first chemotherapy cycle." Mandated in RICOVER-60 and SMARTE-R-CHOP-14. NHL-B1 gave the option of a 5 to 7 day course of prednisone.

Note: Consolidative radiotherapy "given at the discretion of the individual centers (36 to 4500 cGy). Indications for giving radiotherapy after the completion of chemotherapy included bulky disease (greater than or equal to 10 cm) at diagnosis, localized PET-positive residual lesions, and residual disease, not eligible for biopsy at a localized site, and potentially curable by radiotherapy."

1While the primary endpoint in PIX203 was inconclusive (non-inferiority by CR/CRu rate), this arm seemed to have superior OS.
Note: patients in Vose et al. 2001 received rituximab 2 days before CHOP, i.e., all CHOP days are moved forward by 2 days. Patients in GOYA received 8 doses of rituximab, regardless of the number of chemotherapy cycles given. Patients in FLYER were 18 to 60 and had no risk factors according to age-adjusted IPI. Patients in ROBUST could receive two additional cycles of rituximab (8 total), per local practices.

Note: Cunningham et al. 2013 states that the regimen was based on LNH 98-5, but notably it uses prednisolone instead of prednisone. AGMT NHL-14 states that R-CHOP was "given in standard doses" per LNH 98-5, but this regimen uses prednisone, whereas the title and text of Fridrik et al. 2016 imply that prednisolone was used. The authors have confirmed that prednisolone was used, due to prednisone not being available in Austria.

Per investigator discretion, but Cunningham et al. 2013 recommended that patients who had involvement of the "bone marrow, peripheral blood, nasal or paranasal sinuses, orbit, and testis" (they probably intended to say "or testis") receive:

Note: This was the upper bound of cycles specified by Payandeh et al. 2016. In JCOG0601, this regimen was intended for stage I bulky and stage II to IV patients who were younger than 65 years old.

Note: the details for CHOP were not available in the manuscript or supplement; we have reproduced common CHOP dosing, here. For patients achieving CR after cycle 4, the CHOP could be omitted after cycle 6.

Note: in MAIN, CHOP-14 was given for 6 cycles and rituximab for 8 cycles. In Cortelazzo et al. 2016, there was no cap on the vincristine dose, and there was also a discrepancy between the prednisone dose in the body of the manuscript and that in the appendix Figure A1; these discrepancies were clarified by the corresponding author in January 2017. In the abstract of DLCL04, there was no cap on vincristine.

Note: the details for CHOP-14 were not available in the manuscript or supplement; we have reproduced common CHOP-14 dosing, here. For patients achieving CR after cycle 4, the CHOP-14 could be omitted after cycle 6.

Note: This regimen was intended for high-risk DLBCL (IPI greater than or equal to 3). The authors report "excellent outcome" in patients 45 years old or younger, however patients older than 45 years old had "unacceptable mortality."

"Recommended in patients with paraspinal disease, paranasal sinus disease, testicular disease, bone marrow disease, diffuse osseous disease or greater than or equal to 2 sites of extranodal disease. Actual administration of prophylactic intrathecal chemotherapy was at the treating physician's discretion."

Note: This regimen was intended for the treatment of gastric DLBCL only; H. pylori eradication would not be an appropriate treatment for systemic DLBCL. While the regimen is described in Kuo et al. 2012, the cohort described in this paper was treated well after 1996.

Note: Only the dose of liposomal doxorubicin and number of cycles used were specified in the abstract. The doses of the other medications and schedule are provided based on the standard R-CHOP regimen, whose references can be found on this page.

Note: This regimen was intended to reduce cardiotoxicity and was not just for patients with contraindicated doxorubicin. Note that the cycle length was not explicitly defined in the paper but was reported as a median of 21 days (range 21 to 33 days).

Note: This regimen was intended for patients with a contraindication to anthracyclines. Only the dose of etoposide and number of cycles used were specified in the abstract. The doses of the other medications and schedule are provided based on the standard R-CHOP regimen, whose references can be found on this page.

Note: per the paper, "in case patients were non-responsive to R-DHAP but responsive to R-VIM, it was allowed to repeat the R-VIM regimen as the third cycle of reinduction chemotherapy." No statement was made as to whether Mesna was used in the VIM protocol.

1Reported efficacy for TRANSFORM is based on the 2023 update.
Note: Gisselbrecht et al. 2010 refers to the non-randomized regimen described in variant #3 below, although it has slightly different day numbering. Doses are the same. ZUMA-7 & BELINDA described just one dose of rituximab per cycle, given on the day prior to chemotherapy. TRANSFORM also described one dose of rituximab per cycle, given on day 1.

Note: The third cycle was intended to be followed by peripheral blood hematopoietic stem cell collection. ORR reported in Zelenetz et al. 2003 was for the subset of DLBCL patients who received R-ICE; it is unclear if these patients were exposed to rituximab previously. None of the patients in Kewalaramani et al. 2004 had previously received rituximab.

Patients in SHEBA-07-4466-AN-CTIL had primary induction failure or were chemosensitive to salvage therapy. Patients in GELTAMO Z-BEAM LDCGB had primary induction failure or were refractory to salvage therapy.

Note: these are regimens that were generally given with non-curative intent. However, some of these regimens, such as CAR-T therapy, can function as a bridge to consolidation with one of the salvage consolidation regimens, above.

Note: Dose & schedule is as given in Pettengell et al. 2012. CALGB 8552 used a different dose & schedule. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.

We performed a prospective study to investigate the efficacy and safety of triple therapy with aprepitant, ondansetron, and prednisone in non-Hodgkin lymphoma patients receiving R-CEOP or CEOP chemotherapy regimen. All patients were randomly assigned to either an aprepitant regimen (aprepitant plus ondansetron and prednisone), or a control regimen (ondansetron and prednisone) treatment group. For the complete response, the aprepitant group was statistically superior to the control group in the overall study period (76.5% vs. 56.0%; p = .03), as well as in separate analyses of the acute phase (92.2% vs. 78.0%; p = .045), and even more notably in the delayed phase (82.4% vs. 64.0%; p = .037). The overall incidence of adverse events was similar between the two treatment groups (p > .05). The aprepitant regimen was more effective than the control regimen for the prevention of CINV in patients receiving R-CEOP or CEOP regimen and was generally well tolerated.

Background and Objective: Diffuse large B-cell lymphoma (DLBCL), a subtype of non-Hodgkin lymphomas (NHL), is commonly diagnosed in older individuals, and its mortality directly correlates with age. Despite recent advancements in treatment modalities for DLBCL, there is no universally accepted approach for elderly patients. R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) has remained the core therapy for decades but has higher toxicity and lower cure rates in the senior subgroup. This review article discusses the strategies for frailty assessment and subcategorization of the elderly population based on multidomain assessment tools. Further, it outlines potential regimens for the initial treatment of DLBCL based on different levels of frailty.

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