Jan Walewski’s research while affiliated with Maria Skłodowska-Curie Institute of Oncology and other places

The phase 2, multicohort, ongoing ELM-2 study evaluates odronextamab, a CD20×CD3 bispecific antibody, in patients with relapsed/refractory (R/R) B cell non-Hodgkin lymphoma after ≥2 lines of therapy. Here primary analysis of the diffuse large B cell lymphoma (DLBCL) cohort is reported. Patients received intravenous odronextamab in 21-day cycles until progression or unacceptable toxicity, with cycle 1 step-up dosing to mitigate cytokine release syndrome (CRS) risk. The primary endpoint was objective response rate (ORR). Secondary endpoints included complete response (CR) rate, duration of response, progression-free survival (PFS) and overall survival. A total of 127 patients were enrolled. At the 29.9-month efficacy follow-up, the ORR was 52.0% and CR rate was 31.5%. Median durations of response and CR were 10.2 and 17.9 months, respectively. Undetectable minimal residual disease at cycle 4 day 15 was associated with PFS benefit. With a step-up of 0.7 to 4 to 20 mg ( n = 60), CRS was the most common treatment-emergent adverse event (53.3% (grade ≥3, 1.7%)). No immune effector cell-associated neurotoxicity syndrome was reported. Infections were reported in 82/127 (64.6%) patients (grade ≥3, 38.6%; coronavirus disease 2019, 18.1% (grade ≥3, 12.6%)). In conclusion, odronextamab showed encouraging efficacy in heavily pretreated R/R DLBCL and generally manageable safety with supportive care. Clinical trial registration: NCT03888105 .

Burkitt lymphoma is a rare lymphoma entity that represents less than 5% of adult lymphomas. Although prognosis has improved with dose-dense therapy, Burkitt lymphoma remains an area of clinical and biological research with specificities due to the high incidence of CNS involvement and tumour lysis syndrome in patients with a high tumour burden. Few consensus recommendations are available concerning diagnosis, treatment, and prognostic factors in adult patients. In this Review, a European Reference Network on Rare Haematological Diseases (ERN-EuroBloodNet) expert panel has reviewed recent advances in the management of Burkitt lymphoma in the first-line setting to develop updated evidence-based and expert opinion-based recommendations on the management of this disease. The expert panel consisted of ten clinicians and pathologists involved in the clinical management of Burkitt lymphoma from eight EU member states. Additionally, two haematologists were included to support the systematic review process. A balanced representation was ensured between individuals affiliated and not affiliated with ERN-EuroBloodNet. Together with providing current indications on diagnosis and risk-adapted first-line therapy, the Review contains specific recommendations for the identification and management of important complications of Burkitt lymphoma such as tumour lysis syndrome and CNS-oriented therapy, and recommendations for prognostic assessment to guidetreatment. Finally, unresolved questions for Burkitt lymphoma are highlighted, including questions around genetics, imaging, and second-line therapies, along with patient perspective. Your personalized Share Link: https://authors.elsevier.com/c/1kYV7_rV3GEnLV

Traditionally, patients with asymptomatic, advanced‐stage follicular lymphoma were managed with a watchful‐waiting approach until disease progression. The ‘Watch and Wait’ Phase‐3 randomised international trial examined whether rituximab could delay the need for treatment and the effect on quality of life (QoL). In this article, we present the long‐term results of the QoL aspect of the trial. Patients were randomised to watchful‐waiting (Arm A), rituximab induction (Arm B) or rituximab induction followed by maintenance (Arm C). We present the QoL outcomes from 180 patients (Arm A), 188 patients (Arm C) and an exploratory analysis of 82 (Arm B) compared to 81 and 84 patients concurrently randomised to arms A and C. Arm C reported greater improvement in emotional well‐being overtime (Month 37, p = 0.0078) and were significantly more likely to feel in control of their situation than watchful‐waiting patients (Month 25, p = 0.0004; Month 37, p = 0.0476). Watchful‐waiting patients were significantly more likely to avoid thinking about their illness, did not find learning about their illness helped them and were more likely to attach unpleasant connotations to clinic visits (Month 7, p = 0.0032; Month 13, p = 0.0015; Month 25, p = 0.0104). These results demonstrate improved QoL scores in the induction and maintenance rituximab arm, indicating that rituximab was not detrimental to QoL and resulted in an improved QoL in some domains.

Introduction Diffuse large B-cell lymphoma (DLBCL) is an aggressive form of B-cell non-Hodgkin lymphoma (B-NHL). Rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard of care for the first-line (1L) treatment of patients (pts) with DLBCL; however, up to 50% of pts are refractory to or relapse after 1L chemoimmunotherapy, and outcomes worsen with each subsequent relapse (Ip A et al. Adv Ther 2024). In ELM-2 (NCT03888105), odronextamab (an investigational CD20×CD3 bispecific antibody) demonstrated encouraging efficacy and generally manageable safety in pts with relapsed/refractory (R/R) DLBCL who had received ≥2 prior lines of systemic therapy. Median progression-free survival (PFS) and overall survival (OS) in pts with complete response (CR) were 20.4 months (95% CI 12.7-not evaluable [NE]) and not reached (95% CI 17.2-NE), respectively. Grade ≥3 treatment-emergent adverse events (TEAEs) occurred in 84.3% of pts (Ayyappan S et al. ASH 2023). For the current analysis, we present details on the efficacy and safety of 3L+ odronextamab treatment in pts with R/R DLBCL who attained CR in ELM-2. Methods ELM-2 is an ongoing, open-label, multicenter, Phase 2 trial of odronextamab in pts with R/R B-NHL, including a cohort with DLBCL. Intravenous odronextamab was administered in step-up doses with steroid prophylaxis during Cycle (C) 1, followed by 160 mg on Days 1, 8, and 15 of C2-4. After C4, dosing continued at 320 mg once every 2 weeks (Q2W); pts switched to Q4W dosing if they had a durable CR for ≥9 months. The primary endpoint was objective response rate (ORR) according to Lugano classification, by independent central review. Secondary endpoints included CR rate, PFS, OS, duration of response, and safety. Results Primary results in pts with R/R DLBCL evaluable for efficacy and safety (N=127) using the Aug 18, 2023, data cutoff have been reported previously. As of the Oct 20, 2023, data cutoff, median duration of efficacy follow-up was 32.5 months (95% CI 17.4-36.3). The ORR was 52.0% (66/127 pts; 95% CI 42.9-60.9), and the CR rate was 31.5% (40/127; 95% CI 23.5-40.3). Median duration of CR (DOCR) was 17.9 months (95% CI 10.2-NE), and median OS in pts with CR was 38.6 months (95% CI 19.8-NE). Among the 40 pts with CR, median age was 71 years, 1 patient had triple-hit DLBCL, and median duration of treatment exposure was 11.4 months (range 2.6-40.5). Of these pts, 32 had CR at the first response assessment (~Week 12) and 8 reached CR at a later time point, including 2 pts who had stable disease initially. At the time of the current analysis, 8 pts (20.0%) were still receiving treatment, and 32 (80.0%) had discontinued treatment (27 who still had CR at the last response assessment and 5 who had progressive disease). Among the 27 pts with CR who discontinued, the median duration of treatment exposure was 10.1 months (range 2.6-31.5), compared with 4.1 months (0.2-40.5) in the overall study population. Reasons for treatment discontinuation included TEAEs (n=9), physician decision (n=9), death (n=8), and progressive disease (determined by clinical assessment but not confirmed radiologically; n=1). TEAEs included COVID-19 in 3 pts, which was detected 11.0, 26.7, and 31.1 months after treatment initiation. All 8 deaths resulted from TEAEs, including infections and infestations in 7 pts (COVID-19 in 2 pts). Fifteen pts (37.5%) were able to switch to Q4W dosing, 14 of whom still had CR at the last response assessment. In pts who switched to Q4W dosing, the median duration of exposure was 19.8 months (range 15.4-40.5), and 9 pts discontinued treatment. Reasons for treatment discontinuation were physician decision (n=4), TEAEs (n=2), death (n=2, attributed to COVID-19), and progressive disease (n=1). Conclusions Pts with R/R DLBCL and CR to 3L+ odronextamab treatment in ELM-2 had a median DOCR of 17.9 months that was prolonged beyond the median duration of treatment exposure (11.4 months). Over a third (37.5%) of pts proceeded to monthly odronextamab administration, with a median duration of treatment exposure of 19.8 months. The findings reported here show the sustainability of CR in pts with DLBCL treated with 3L+ odronextamab and demonstrate the generally manageable safety profile of odronextamab despite prolonged drug exposure, thus supporting the potential of odronextamab as a treatment for R/R DLBCL.

Introduction Other aggressive B-NHL encompasses multiple rare subtypes (e.g., primary mediastinal B-cell lymphoma [PMBL], high-grade B-cell lymphoma [HGBL], and follicular lymphoma [FL] Grade 3b) that demonstrate rapid disease progression and poor prognosis, especially in the relapsed/refractory (R/R) setting. Importantly, these subtypes are often excluded from enrollment in studies of R/R diffuse large B-cell lymphoma (DLBCL); therefore, clinical trial experience with novel agents is limited. Odronextamab, an investigational, off-the-shelf, CD20×CD3 bispecific antibody, has shown compelling efficacy and generally manageable safety in various B-NHL subtypes in the ELM-1 study (Bannerji R et al. Lancet Haematol 2022). ELM-2 (NCT03888105) is an ongoing, global, open-label, Phase 2 study evaluating the efficacy and safety of odronextamab in patients with R/R B-NHL. Here, we report the first preliminary results from the other aggressive B-NHL cohort of the ELM-2 study. Methods Patients aged ≥18 years with ECOG PS 0-1, adequate organ function, and aggressive B-NHL subtypes (excluding DLBCL and mantle cell lymphoma) that relapsed or were refractory after ≥2 prior lines of systemic therapy were eligible for enrollment. Odronextamab was given intravenously with steroid prophylaxis and step-up dosing in Cycle (C) 1 (each cycle=21 days) that was optimized to help mitigate the risk of cytokine release syndrome (CRS). Patients received odronextamab 160 mg on Days 1, 8, and 15 of C2-4, then maintenance dosing of 320 mg Q2W post-C4 until disease progression or unacceptable toxicity. Patients with a complete response (CR) for ≥9 months switched to Q4W dosing. Infection prophylaxis, including IVIG supplementation, PJP prophylaxis, and antivirals, was recommended for all patients. The primary endpoint was objective response rate (ORR) by independent central review according to Lugano classification. Secondary endpoints included ORR by local investigator, duration of response (DOR), progression-free survival, overall survival, and safety. Results At data cutoff (May 2, 2024), 49 patients with R/R aggressive B-NHL were enrolled, including HGBL, NOS (n=9); PMBL (n=8); FL Grade 3b (n=7); mixed histology B-NHL (n=4); Burkitt lymphoma (n=3); EBV+ DLBCL (n=3); HGBL with MYC and BCL-2 and/or BCL-6 rearrangements (n=3); T-cell/histiocyte-rich large B-cell lymphoma (n=3); and others (n=9). Forty-six patients were evaluable for efficacy. The median follow-up was 12.0 (95% CI 8.2-21.1) months. Overall, the median age was 58 years (range 24-83), and 59.2% of patients were male. Patients had received a median of 3 (range 2-9) prior lines of therapy, with 69.4% refractory to their last therapy, and 61.2% double refractory. Median odronextamab exposure was 19.0 weeks (range 2.0-131.9); 98.0% of patients completed C1 and 65.3% completed ≥4 treatment cycles. The ORR in efficacy-evaluable patients was 60.9% (95% CI 45.4-74.9), and the CR rate was 43.5% (95% CI 28.9-58.9), by local investigator assessment. The median DOR was not reached (95% CI 4.8 months-not evaluable); 36-month DOR was 54.3% (95% CI 27.5-75.0). In all patients, the most common treatment-emergent adverse events (TEAEs) of any grade were CRS (53.1%), anemia (42.9%), and pyrexia (30.6%). Grade ≥3 TEAEs occurred in 81.6% of patients, the most common being anemia (20.4%) and neutropenia (22.4%). CRS occurred in 51.4% (18/35) of patients who received the optimized 0.7/4/20 mg step-up regimen: Grade 1, 40.0% (n=14); Grade 2, 8.6% (n=3); Grade 3, 2.9% (n=1). No cases of ICANS were reported. Grade ≥3 infections occurred in 15 patients (38.8%), with 2 Grade 5 cases; 24.5% of all patients had COVID-19 infection. Five patients (10.2%) discontinued treatment due to TEAEs. No new safety signals were observed. Conclusions Odronextamab showed promising efficacy in heavily pretreated patients with rare subtypes of R/R aggressive B-NHL, achieving an ORR of 60.9% and CR rate of 43.5%. Responses were durable, with 54.3% maintaining response at 3 years. The safety profile of odronextamab was generally manageable and consistent with previous reports of bispecific antibodies in lymphoma, with no new safety concerns identified. These findings support the potential role of odronextamab in the treatment paradigm for rare subtypes of R/R aggressive B-NHL. Updated data, including efficacy in each subtype, will be presented.

Introduction Odronextamab, a novel, investigational, CD20×CD3 bispecific antibody, has demonstrated compelling efficacy and a generally manageable safety profile in heavily pretreated patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) in the CAR-T-naïve and post-CAR-T therapy settings (Ayyappan S et al. ASH 2023; Crombie J et al. ASH 2023). Here, we report long-term efficacy and safety data for odronextamab from a pooled analysis of the DLBCL post-CAR-T cohort in the ELM-1 study (NCT02290951), which was the only pivotal study of a bispecific antibody with a prespecified cohort dedicated to this population, and the CAR-T-naïve DLBCL cohort in the ELM-2 study (NCT03888105). Methods Odronextamab was administered intravenously in 21-day cycles. A step-up dosing regimen with steroid prophylaxis was employed during Cycle 1, followed by 160 mg on Days 1, 8, and 15 of Cycles 2-4. Maintenance therapy consisted of 320 mg every 2 weeks until disease progression or unacceptable toxicity. Patients with durable complete response (CR) for ≥9 months transitioned to dosing every 4 weeks. The primary endpoint was objective response rate (ORR) by independent central review (ICR) using the Lugano classification. Key secondary endpoints included CR rate, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Results The analysis set consisted of a pooled population of 187 patients with R/R DLBCL from ELM-1 (n=60; data cutoff date of January 22, 2024) and ELM-2 (n=127; data cutoff date October 20, 2023). Median duration of follow-up was 23.0 months. Median age was 65.0 years (range 24-88), 61.5% of patients were male, 78.6% had Ann Arbor stage III-IV, 56.7% had an IPI score ≥3, and the median number of prior lines of therapy was 3 (range 2-9). The 60 patients included from ELM-1 had all received prior CAR-T therapy, representing 32.1% of the total pooled population (60/187), and of these, 48.3% (29/60) had relapsed within ≤90 days of initiating CAR-T therapy, and 71.7% (43/60) had CAR-T-refractory disease. Overall, 83.4% of the pooled population had disease that was refractory to the last line of therapy. Median duration of odronextamab exposure was 14.7 weeks; 91.4% (171/187) of the population completed ≥1 cycle, and 59.4% (111/187) completed ≥4 cycles. ORR and CR rate confirmed by ICR were 50.8% (95/187) and 31.6% (59/187), respectively, and were generally consistent across multiple high-risk subgroups, including the post-CAR-T therapy subgroup. Median DOR was 10.5 months (95% CI 5.4-24.8) and median duration of CR was 36.3 months (95% CI 12.4-not evaluable); the probability of maintaining CR for 36 months was 51.0%. The probability of PFS and OS at 36 months was 17.5% and 27.0%, respectively. Safety was generally consistent with previous reports. The most common treatment-emergent adverse events (>30% all grades) were cytokine release syndrome (CRS; 52.9%), anemia (35.8%), pyrexia (39.6%), and neutropenia (31.6%). Adverse events led to treatment discontinuation in 25 patients (13.4%). With the optimized 0.7/4/20 mg step-up regimen (n=100), 48.0% of patients (48/100) had CRS events that were Grade (Gr) 1/2, and one Gr 3 CRS event (confounded by pancreatitis) was reported. All CRS events resolved with supportive measures. No immune effector cell-associated neurotoxicity syndrome events were reported with the 0.7/4/20 mg step-up regimen. Gr ≥3 infections occurred in 46 patients (24.6%; Gr 5, n=16 [8.6%]). COVID-19 infections were reported in 30 patients (16.0%), of which Gr 5 was reported in 6 patients (3.2%). Conclusions This pooled analysis of patients with R/R DLBCL from the ELM-1 and ELM-2 studies, which represents the largest dataset reported for a bispecific antibody in the third-line or later setting, confirms that with longer follow-up the recommended odronextamab dose retains highly encouraging efficacy. Responses were durable, with a 51% probability of maintaining CR for 3 years. The safety profile was generally consistent with earlier reports and CRS events with the 0.7/4/20 mg step-up dosing regimen were predominantly low grade and generally manageable. Importantly, continued treatment with odronextamab demonstrated no detrimental effects on survival outcomes over a longer follow-up period. Odronextamab may be an important potential option in future management of R/R DLBCL, and Phase 3 trials are ongoing. Updated data will be presented.

On behalf of the European MCL Network, ML and EH contributed equally Introduction: In younger patients with mantle cell lymphoma (MCL), the addition of ibrutinib during induction immuno-chemotherapy and as 2-years maintenance with and without autologous stem cell transplantation (ASCT) has shown high efficacy in the 3-arm randomized TRIANGLE trial (Dreyling et al., Lancet 2024), establishing a new standard of care induction treatment and maintenance. However, the efficacy comparison of the two ibrutinib-containing treatment arms with and without ASCT was still ongoing. With prolonged follow-up, we now aim to clarify the role of ASCT in the context of ibrutinib-containing treatment, to confirm the previously observed treatment effects and to perform overall survival (OS) comparisons. Patients and methods: In 2016, the European MCL Network initiated the randomized, open-label, 3-arm TRIANGLE trial to evaluate the addition of ibrutinib to standard treatment with ASCT (arm A+I) in comparison to the previous standard treatment (arm A) and an ibrutinib-containing treatment without ASCT (arm I). Patients with previously untreated, advanced stage II-IV MCL, up to 65 years, and suitable for high-dose cytarabine and ASCT, were randomized 1:1:1 to the 3 trial arms in 13 European countries and Israel. Study treatment consisted of 6 alternating cycles of R-CHOP and R-DHAP without (arm A) or with ibrutinib added to R-CHOP cycles and as 2 years maintenance (arms A+I, I). ASCT was planned for patients of arms A and A+I responding to induction therapy. Rituximab maintenance was recommended to be applied according to national guidelines in responding patients of each trial arm. For the primary outcome, failure-free survival (FFS), stable disease at the end of induction, progression, or death were counted as events. Three pairwise log-rank tests for FFS were monitored with regular pre-planned interim analyses, each maintaining a one-sided 1.67% significance level. A pre-defined decision criterion based on the statistical significance of the treatment comparisons for FFS was established to determine the future treatment recommendation. In 2022, arm A had failed to show FFS-superiority over I and FFS in arm A+I was shown to be superior to A. OS was a secondary outcome and formal pairwise OS comparisons between treatment arms were pre-planned with interim analyses based on O'Brien-Fleming boundaries to maintain pairwise two-sided 5% significance levels. Results: Between July 2016 and December 2020, 870 patients were randomized to arms A (n=288), A+I (n=292), and I (n=290). Median age was 57 years (range 27-68), 76% were male, 87% had stage IV, and 58%/27%/15% had low/intermediate/high risk MIPI. After a median follow-up of 53 months, A+I failed to show FFS-superiority over I (3-year FFS A+I: 86% vs. I: 85%; one-sided p=0.28, hazard ratio: 0.87). FFS-superiority of A over I was again not confirmed with 3-year FFS 75% (A) vs. 85% (I; one-sided p=0.9942, hazard ratio: 1.38). In contrast, the retrospectively calculated two-sided p-value on an overall 5% significance level was consistent with FFS-superiority of I over A (p=0.0102). FFS-superiority of A+I over A was again confirmed with 3-year FFS 86% (A+I) vs. 75% (A; one-sided p=0.0034, hazard ratio: 0.64). Compared with arm A (3-year OS 85%), OS was prolonged in arms A+I and I with 3-year OS of 90% in A+I (p=0.0069, hazard ratio 0.61), and 91% in I (p=0.0041, hazard ratio 0.59). Conclusions: The results confirm superiority of ibrutinib-containing treatment without ASCT (arm I) over ASCT-containing treatment without ibrutinib (arm A) in terms of both, FFS and OS. In the context of ibrutinib- and high-dose cytarabine-containing induction immuno-chemotherapy and ibrutinib maintenance, the addition of ASCT failed to show FFS superiority, while increasing toxicity during maintenance/follow-up. According to the pre-defined decision strategy, ibrutinib+R-CHOP/R-DHAP induction followed by 2 years of ibrutinib maintenance should be the new standard of care in younger MCL patients, thus ending the era of ASCT for MCL patients.

Introduction The TRIANGLE trial (Dreyling et al. 2024) has set a novel standard in first-line treatment of mantle cell lymphoma (MCL) patients aged 18-65 years, highlighting the role of ibrutinib in the management of these patients. During the planning stage of TRIANGLE, results of the LYSA-LYMA trial showed a progression-free survival (PFS) benefit with rituximab maintenance (Rm) after a cytarabine-containing induction and autologous stem cell transplantation (ASCT) in younger patients with MCL (Le Gouill et al. 2017). Therefore, the TRIANGLE trial recommended from the beginning the additional non-randomized administration of Rm (every two months for 3 years) to all three treatment arms (arm I: IR-CHOP/ R-DHAP+ Im; arm A+I: IR-CHOP/ R-DHAP followed by ASCT + Im; arm A, i.e. pre-trial standard of care: R-CHOP/ R-DHAP followed by ASCT) according to national guidelines and/or center practice. We retrospectively analyzed the TRIANGLE data to assess the efficacy and toxicity of additional Rm to ibrutinib-containing regimens, with and without ASCT, and to independently confirm the LYSA-LYMA results in younger, untreated MCL patients. Methods All patients in remission after induction therapy (arm I) and after ASCT (arms A+I, A) were included in this analysis and assigned to Rm or noRm groups based on the as-treated principle. Every treatment arm (arm I,arm A+I, and arm A) was evaluated separately, thus, no adjustment of the alpha level was necessary. The primary endpoint PFS from end of induction (arm I)/end of ASCT (arm A+I, A) was summarized using Kaplan-Meier curves. Differences between Rm and noRm groups within each treatment arm were evaluated using a two-sided log-rank test with an alpha level of 0.05. To address baseline imbalances and to increase power, Cox regression models were calculated including MCL International Prognostic Index (MIPI) (Hoster et al. 2008), response status at the end of induction therapy (CR vs PR after induction/ASCT), Ki67,and cytology (classical vs.pleomorphic/blastoid variant). Results In the different study arms, 59% (n=159; arm I), 64% (n=151; arm A+I) and 67% (n=155; arm A) started Rm. In general, baseline characteristics were well balanced between the Rm and noRm groups in all treatment arms except for more frequent pleomorphic/blastoid cytology in the noRm group of arm I; higher Ki67 in the Rm group of arm A and A+I; and a higher Ann-Arbor stage, and more frequent CR after ASCT in the noRm group of arm A. After a median follow-up time of 4.0 years, median duration of Rm, excluding patients who relapsed, died, or withdrew, was 26 months for arm I and 30 months for arms A+I and A. The Kaplan-Meier curves for PFS and adjusted Cox regression analyses indicated a significantly longer PFS with additional Rm administration in all three treatment arms. The adjusted hazard ratio (Rm vs. noRm) for arm I was 0.50 (95% CI: 0.28 - 0.90, p-value 0.019), for arm A+I 0.26 (95% CI: 0.13 - 0.51, p-value <0.001), and for arm A 0.29 (95% CI: 0.16 - 0.52, p-value <0.001), respectively. Accordingly, the 4-year PFS rate estimated from the Kaplan-Meier curves were for arm I 86% (95% CI: 80% - 92%) in the Rm group vs. 76% (95% CI: 67% - 85%; log rank p=0.016) in the noRm group, for arm A+I 89% (95% CI: 84% - 95%) in the Rm group vs. 75% (95% CI: 65% - 87%; log rank p <0.001) in the noRm group; and for arm A 83% (95% CI: 77% - 89%) in the Rm group vs. 54% (95% CI: 42% - 68%; log-rank p <0.001) in the noRm group. Rm was associated with a modest increase in infectious complications (grade 3 or greater) in all arms (arm I: 25% in the Rm group vs. 12% in the noRm group; arm A+I: 30% in the Rm group vs. 13% in the noRm group; arm A: 19% in the Rm group vs. 1% in the noRm group). In contrast hematological toxicity (grade 3 or greater) was increased only in arm A (28% in the Rm group vs. 11% in the noRm group), whereas comparable frequencies were observed in the other study arms (arm A+I: 46% in the Rm group vs. 52% in the noRm group; arm I: 27% in the Rm group vs 23% in the noRm group). Conclusion This analysis confirms the benefit of Rm, as single maintenance (arm A) as well as in combination with ibrutinib (arms A+ I and I). No unexpected toxicity signals were observed, supporting its use also in combination with novel regimens. On behalf of the European MCL Network *: shared first/senior authorship

During a fatal disease, patients often request updated information on their prognosis. After patients have already survived a certain time, conditional survival captures their future survival probability. We investigated conditional overall and failure‐free survival in 473 younger mantle cell lymphoma (MCL) patients from a randomized phase III trial comparing immunochemotherapies R‐CHOP and alternating R‐CHOP/R‐DHAP before autologous transplantation. Using conditional Kaplan–Meier method and Cox regression, we estimated subsequent survival of patients who had survived 1–8 years, considering MIPI, Ki‐67, and treatment failure status. Starting at a lower level, R‐CHOP patients only showed increasing subsequent survival as they survived longer (5‐year conditional survival: 72% and 81% after surviving 1 and 7 years), while R‐CHOP/R‐DHAP patients had stable future survival over time (77% and 78%). The prognostic value of MIPI diminished after 3 years in R‐CHOP patients but remained unchanged after R‐CHOP/R‐DHAP. Patients with treatment failure had markedly inferior survival compared with those in ongoing remission, regardless of the time survived. The longer patients remained in remission, the longer they would stay free of treatment failures. Our results enable personalized counselling for younger MCL patients by offering dynamic prognosis and underscore the importance of highly effective first‐line treatment to improve survival.