Late relapse in patients with diffuse large B‐cell lymphoma: impact of rituximab on their incidence and outcome

Vannata, Barbara; Conconi, Annarita; Winkler, Jonas; Cascione, Luciano; Casaluci, Gloria Margiotta; Nassi, Luca; Moia, Riccardo; Pirosa, Maria Cristina; Moccia, Alden A.; Stathis, Anastasios; Rossi, Davide; Gaïdano, Gianluca; Zucca, Emanuele

doi:10.1111/bjh.16106

Cited by 11 publications

(10 citation statements)

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“…Given that it remains unclear which therapies may be useful in patients who have a relapse after the receipt of axi-cel, these additional data, together with real-world outcomes and clinical trials, may help inform treatment decisions in the future. 32 Whereas the majority of patients with large B-cell lymphoma have a relapse less than 12 months after the receipt of induction therapy in the post-rituximab era, 33,34 this trial did not enroll patients with large B-cell lymphoma relapse that occurred more than 12 months after the receipt of induction therapy. Relapses occurring later after induction therapy are generally associated with a greater probability of response to second-line therapy.…”

Section: Discussionmentioning

confidence: 99%

Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma

et al. 2022

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BACKGROUNDThe prognosis of patients with early relapsed or refractory large B-cell lymphoma after the receipt of first-line chemoimmunotherapy is poor. METHODSIn this international, phase 3 trial, we randomly assigned, in a 1:1 ratio, patients with large B-cell lymphoma that was refractory to or had relapsed no more than 12 months after first-line chemoimmunotherapy to receive axicabtagene ciloleucel (axi-cel, an autologous anti-CD19 chimeric antigen receptor T-cell therapy) or standard care (two or three cycles of investigator-selected, protocol-defined chemoimmunotherapy, followed by high-dose chemotherapy with autologous stem-cell transplantation in patients with a response to the chemoimmunotherapy). The primary end point was event-free survival according to blinded central review. Key secondary end points were response and overall survival. Safety was also assessed. RESULTSA total of 180 patients were randomly assigned to receive axi-cel and 179 to receive standard care. The primary end-point analysis of event-free survival showed that axi-cel therapy was superior to standard care. At a median follow-up of 24.9 months, the median event-free survival was 8.3 months in the axi-cel group and 2.0 months in the standard-care group, and the 24-month event-free survival was 41% and 16%, respectively (hazard ratio for event or death, 0.40; 95% confidence interval, 0.31 to 0.51; P<0.001). A response occurred in 83% of the patients in the axi-cel group and in 50% of those in the standard-care group (with a complete response in 65% and 32%, respectively). In an interim analysis, the estimated overall survival at 2 years was 61% in the axi-cel group and 52% in the standardcare group. Adverse events of grade 3 or higher occurred in 91% of the patients who received axi-cel and in 83% of those who received standard care. Among patients who received axi-cel, grade 3 or higher cytokine release syndrome occurred in 6% and grade 3 or higher neurologic events in 21%. No deaths related to cytokine release syndrome or neurologic events occurred. CONCLUSIONSAxi-cel therapy led to significant improvements, as compared with standard care, in event-free survival and response, with the expected level of high-grade toxic effects. (Funded by Kite; ZUMA-7 ClinicalTrials.gov number, NCT03391466.

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Section: Discussionmentioning

confidence: 99%

Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma

et al. 2022

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“…The outcomes depend on the relapse timing, as patients with early relapse show significantly poor compared to patients with late relapse [ 19 ]. For instance, in the CORAL study, patients with the relapsed disease within 12 months showed substantially lower response rate (46% vs. 88%), 3-year event-free survival rate (20% vs. 45%), and 3-year OS rate (39% vs. 64%) compared to patients with relapsed disease after 12 months when treated with rituximab combined with either ICE or DHAP [ 7 ].…”

Section: Discussionmentioning

confidence: 99%

Outcomes in Refractory Diffuse Large B-Cell Lymphoma: Results from Two Prospective Korean Cohorts

Jeong

Kim

et al. 2023

Cancer Res Treat

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Purpose Diffuse large B-cell lymphoma (DLBCL) is the most common hematologic malignancy worldwide. Although substantial improvement has been achieved by the frontline rituximab-based chemoimmunotherapy, up to 40%-50% of patients will eventually have relapsed or refractory disease, whose prognosis is extremely dismal.Materials and Methods We have carried out two prospective cohort studies that include over 1,500 DLBCL patients treated with rituximab plus CHOP (#NCT01202448 and #NCT02474550). In the current report, we describe the outcomes of refractory DLBCL patients. Patients were defined to have refractory DLBCL if they met one of the followings, not achieving at least partial response after 4 or more cycles of R-CHOP; not achieving at least partial response after 2 or more cycles of salvage therapy; progressive disease within 12 months after autologous stem cell transplantation.Results Among 1,581 patients, a total of 260 patients met the criteria for the refractory disease after a median time to progression of 9.1 months. The objective response rate of salvage treatment was 26.4%, and the complete response rate was 9.6%. The median overall survival (OS) was 7.5 months (95% confidence interval, 6.4 to 8.6), and the 2-year survival rate was 22.1%±2.8%. The median OS for each refractory category was not significantly different (p=0.529).Conclusion In line with the previous studies, the outcomes of refractory DLBCL patients were extremely poor, which necessitates novel approaches for this population.

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“…Second-line treatment was presumed to be for relapsed disease in 9% and for primary refractory disease in 7%. The reported incidence of relapsed/refractory DLBCL patients ranges between 17% and 30%, with up to 10% after EFS24 ( 15 , 18 , 38 , 61 , 62 ). This discrepancy with our cohort probably relies on 2 main factors.…”

Section: Discussionmentioning

confidence: 99%

Real-World Estimation of First- and Second-Line Treatments for Diffuse Large B-Cell Lymphoma Using Health Insurance Data: A Belgian Population-Based Study

Daneels

Rosskamp²,

Macq³

et al. 2022

Front. Oncol.

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We determined first- and second-line regimens, including hematopoietic stem cell transplantations, in all diffuse large B cell lymphoma (DLBCL) patients aged ≥20 yr (n = 1,888), registered at the Belgian Cancer Registry (2013–2015). Treatments were inferred from reimbursed drugs, and procedures registered in national health insurance databases. This real-world population-based study allows to assess patients usually excluded from clinical trials such as those with comorbidities, other malignancies (12%), and advanced age (28% are ≥80 yr old). Our data show that the majority of older patients are still started on first-line regimens with curative intent and a substantial proportion of them benefit from this approach. First-line treatments included full R-CHOP (44%), “incomplete” (R-)CHOP (18%), other anthracycline (14%), non-anthracycline (9%), only radiotherapy (3%), and no chemo-/radiotherapy (13%), with significant variation between age groups. The 5-year overall survival (OS) of all patients was 56% with a clear influence of age (78% [20–59 yr] versus 16% [≥85 yr]) and of the type of first-line treatments: full R-CHOP (72%), other anthracycline (58%), “incomplete” (R-)CHOP (47%), non-anthracycline (30%), only radiotherapy (30%), and no chemo-/radiotherapy (9%). Second-line therapy, presumed for refractory (7%) or relapsed disease (9%), was initiated in 252 patients (16%) and was predominantly (71%) platinum-based. The 5-year OS after second-line treatment without autologous stem cell transplantation (ASCT) was generally poor (11% in ≥70 yr versus 17% in <70 yr). An ASCT was performed in 5% of treated patients (n = 82). The 5-year OS after first- or second-line ASCT was similar (69% versus 66%). After adjustment, multivariable OS analyses indicated a significant hazard ratio (HR) for, among others, age (HR 1.81 to 5.95 for increasing age), performance status (PS) (HR 4.56 for PS >1 within 3 months from incidence), subsequent malignancies (HR 2.50), prior malignancies (HR 1.34), respiratory and diabetic comorbidity (HR 1.41 and 1.24), gender (HR 1.25 for males), and first-line treatment with full R-CHOP (HR 0.41) or other anthracycline-containing regimens (HR 0.72). Despite inherent limitations, patterns of care in DLBCL could be determined using an innovative approach based on Belgian health insurance data.

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Late relapse in patients with diffuse large B‐cell lymphoma: impact of rituximab on their incidence and outcome

Cited by 11 publications

References 58 publications

Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma

Axicabtagene Ciloleucel as Second-Line Therapy for Large B-Cell Lymphoma

Outcomes in Refractory Diffuse Large B-Cell Lymphoma: Results from Two Prospective Korean Cohorts

Real-World Estimation of First- and Second-Line Treatments for Diffuse Large B-Cell Lymphoma Using Health Insurance Data: A Belgian Population-Based Study

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