Chronic lymphocytic leukemia (CLL) is a disease that primarily affects older patients, with a median age at diagnosis of 72 years. Older patients, in this review defined as 80 years or older, comprise about 20

Background: Progression-free survival (PFS) is strongly correlated with overall survival (OS) after time-limited first-line treatment of chronic lymphocytic leukemia (CLL). Current CLL guidelines recommend a switching of drug classes after “early” PD, while patients (pts) with “late” PD may be re-treated with prior therapy. However, the definition of early vs. late PD varies widely (12-36 months after end of treatment [EOT]) and remains under debate. Methods: Seven randomized phase III trials of the German CLL Study Group (GCLLSG) comprising 3,829 pts who received at least one dose of study medication were analyzed. Included studies were CLL4, CLL5, CLL8, CLL10, CLL11, CLL13 and CLL14. 2,921 pts (76.3%) were treated with CIT (bendamustine + rituximab (R), fludarabine +/- cyclophosphamide +/- R; chlorambucil, chlorambucil + R or + obinutuzumab (O)) and 908 with TT (23.7%) (venetoclax + O, venetoclax + R, venetoclax + O + ibrutinib). CIT was administered for a maximum of 6 cycles. TT duration was 12-36 cycles, with 23 pts (2.5%) treated beyond 15 cycles of therapy. Pts were grouped by first-line treatment received (chemo(immuno)therapy [CIT] vs. targeted therapy [TT]). Cox proportional hazards models were estimated for OS from EOT for various thresholds regarding timing of PD, with both PD as categorical covariate (i.e. early, late, and no PD) and time to PD from EOT as time-dependent continuous covariate. The optimal threshold for defining early PD after EOT was determined by the maximum standardized difference in hazard between early and late PD (assessed via z-value) and the maximum model fit. Hazard ratios (HR) were calculated for early and late vs. no PD. Multivariable multinomial regression analyses were performed to determine associations of early and late vs. no PD with known risk factors. Results: After a median observation time of 65 months from EOT, 2,131 (55.7%) pts experienced PD, and 1,143 (29.9%) pts died. Most PD events (1,435 [67.3%|) occurred >12 months after EOT. PD occurred in 1,837 pts (62.9%) treated with CIT and in 294 pts (32.4%) treated with TT. A 12-month cutoff after EOT was identified as the most effective threshold to distinguish early from late PD with respect to OS. This timepoint showed the largest difference in mortality risk between early and late PD (z-value: 8.72) and yielded the best model fit. The same 12-month threshold was confirmed in subgroup analyses of pts treated with CIT (z = 7.42) and TT (z = 3.84), supporting its consistency across treatment modalities. Overall, 696 pts (18.2%) experienced early PD (≤12 months after EOT). These pts had significantly worse OS compared to those without PD (HR 5.43, 95% CI 4.66–6.33, p<0.001). Late PD (beyond 12 months) was also associated with shorter OS, but to a lesser extent (HR 2.52, 2.09–3.04, p<0.001). For CIT, early PD was associated with an HR of4.57 (3.89–5.37, p<0.001) and late PD with an HR of 2.35 (1.94–2.86, p<0.001). In the TT group, early PD was associated with a higher risk of death (HR 9.23, 5.16 – 16.5, p<0.001), whereas late PD was not significantly different from no PD (HR 1.73, 0.81 – 3.71, p=0.157). When analyzing time to PD from study entry (instead of EOT), early PD occurring before 18 months (CIT) or 24 months (TT) was associated with the highest mortality risk, respectively, supporting the 12-month threshold after EOT as a meaningful definition for early PD. Multivariable multinomial regression analyses identified factors associated with early PD. For CIT, these included unmutated IGHV, TP53 aberrations, del(11q), abscence of B-symptoms, CIRS score >6 and creatinine clearance <70ml/min. For TT, unmutated IGHV and TP53 aberrationswere associated with early PD. However, in multivariable Cox proportional hazards analyses, neither IGHV (HR 1.52, 0.91 – 2.5, p=0.108) nor TP53 status (HR 1.65, 0.71 – 3.87, p=0.245) were prognostic for OS after EOT. Conclusion: This analysis challenges the current definition of early vs. late PD commonly used in CLL treatment guidelines in the context of targeted fixed-duration therapy. Pts who experience PD within 12 months after stopping treatment have a significantly higher risk of death, independent of TP53 aberrations and IGHV mutational status, highlighting the high-risk nature of early PD. This group may represent a distinct high-risk population warranting further clinical investigation and tailored treatment strategies.

ABSTRACT:Because frail patients and patients aged ≥80 years with chronic lymphocytic leukemia (CLL) are still underrepresented in clinical trials, the CLL-Frail trial aimed to evaluate the efficacy and safety of acalabrutinib in these patients. The primary end point was the overall response rate (ORR) after 6 cycles of treatment to test the null hypothesis of ORR ≤65%. Fifty-three patients were included in the trial, and 34 patients are still on therapy. Adverse events (AEs) were the most frequent reason for early discontinuation (10 patients), whereas 5 patients stopped treatment because of death. Median age was 81 years, and 47.2% of patients were frail. The ORR for the 46 patients receiving ≥3 cycles of treatment was 93.5% (95% confidence interval, 82.1-98.6) meeting the primary end point of this trial (P < .001). The estimated 12-month progression-free and overall survival rates were 93.3% and 95.7%, respectively, after a median follow-up of 19 months. 53.5% of patients reported an improvement in their self-perceived frailty. Although all patients experienced AEs, and severe (Common Terminology Criteria of ≥3) events were reported in 63.5% of patients, there were no events of severe bleeding and atrial fibrillation was rare (2 cases of Common Terminology Criteria Grades 2 and 3). Five patients died, of which 4 deaths happened during or <28 days after treatment. Infections/COVID-19 were the cause of death in 3 cases. To our knowledge, this is the first prospective trial in older and/or frail patients with CLL demonstrating a high efficacy and safe treatment with acalabrutinib monotherapy. This trial was registered at www.ClinicalTrials.gov as #NCT04883749.

The increasing use of immunotherapeutic approaches, cellular therapies, and targeted agents is rapidly and profoundly changing the treatment paradigms of haematological malignancies. These novel therapies are increasingly incorporated into earlier lines of treatment. Some are administered for a fixed duration, often with curative intent, whereas others are administered chronically for disease control. The associated acute, mid-term, and long-term toxic effects can differ markedly from conventional cytotoxic chemotherapy and radiotherapy. Accumulating clinical experience and data enable identification of class-specific effects and development of consensus-based guidelines for toxicity management. In this third paper in the Series on adverse event reporting, we build on our emerging understanding of toxicity profiles of novel treatments to propose an actionable framework for improved assessment, reporting, and critical appraisal of treatment tolerability. We discuss recent insights regarding second cancers and the relevance of infectious complications, explore tolerability aspects of time-limited treatments, and suggest approaches to address gaps in tolerability assessment.

Introduction Current treatment for chronic lymphocytic leukemia (CLL) follows two seminal paradigms: continuous Bruton tyrosine kinase inhibitor (BTKi) therapy until progression and fixed-duration regimens combining BCL2 inhibitors with a CD20 antibody or BTKi, typically given over one year. These two different approaches were established through comparisons to chemo(immuno)therapy and are yet to be compared directly. Here we present data of a prospective trial comparing continuous ibrutinib (I) monotherapy to fixed-duration venetoclax plus obinutuzumab (VO) and venetoclax plus ibrutinib (VI) for CLL. Methods CLL17 (NCT04608318) is an investigator-initiated, international, randomized phase 3 trial for patients (pts) with previously untreated CLL. Pts were randomized to receive ibrutinib (I), fixed-duration venetoclax plus obinutuzumab (VO) or fixed-duration venetoclax plus ibrutinib (VI). Randomization was stratified by IGHV status, del(17p)/TP53mut and patient fitness, defined by cumulative illness rating scale (CIRS) score >6 and/or creatinine clearance <70 mL/min. Ibrutinib was given continuously until intolerance or progression; VO consisted of 6 cycles (28 days each) of venetoclax plus obinutuzumab, followed by 6 additional cycles of venetoclax monotherapy; VI was initiated with a 3-cycle ibrutinib lead-in, followed by 12 cycles of VI. The study was designed to test non-inferiority of VO vs I and VI vs I. The primary endpoint was investigator-assessed progression-free survival (PFS). A ≤8% reduction in 3-year (yr) PFS was deemed not clinically meaningful (non-inferiority HR margin 1.608). Per protocol, an interim analysis was planned once 65% of required PFS events (138 of 213) were reached. Secondary endpoints included overall response rate (ORR), undetectable minimal residual disease (uMRD), overall survival (OS) and safety. Results In total, 909 pts were randomized to VO (N=303), VI (N=305), and I (N=301). Data cut-off was on April 11th, 2025, median observation time was 34.2 months (range 0-49). Median age was 66 yrs (34-90), 67.8% were male, median CIRS score was 3 (0-18); 33.7% had a creatinine clearance <70 mL/min. Overall, 7.6% had del(17p) and/or TP53 mutation, 56.5% unmutated IGHV and 19.2% complex karyotype (≥3 aberrations); 53.8% and 6.5% had high or very high CLL-IPI, respectively. Three-yr PFS was 81.1% in the VO arm compared to 81.0% in the I arm (HR 0.87, type-I-error adjusted CI [98.3%] 0.54-1.41) and 79.4% in the VI arm (compared to I arm: HR 0.84, type-I-error adjusted CI [98.0%] 0.53-1.32), respectively, with the upper limit of each adjusted CI below the pre-defined non-inferiority margin, providing early evidence of non-inferiority. At final staging (C18D1), the ORR was 84.2% in the VO arm, 88.5% in the VI arm, and 86.0% in the I arm, with a CR rate of 51.5%, 46.2%, and 8.3%, respectively; the uMRD (<10-4) rate in ITT population in peripheral blood was 73.3% (62.0% in bone marrow) in the VO arm, 47.2% (40.0% in bone marrow) in the VI arm and 0% (0% in bone marrow) in the I arm. At 3 yrs, the OS rate was 91.5% in the VO arm, compared to 95.7% in the I arm (HR 1.67, 95% CI 0.86-3.28) and 96.0% in the VI arm (compared to I: HR 0.96, 95%CI 0.45-2.05), respectively. For pts with unmutated IGHV, 3-yr PFS in the VO arm was 75.8% (87.6% for mutated IGHV) compared to 79.7% (83.5%) in the I arm (HR 0.98, 95% CI 0.61-1.59), and 78.9% (80.0%) in the VI arm (compared to I: HR 0.81, 95% CI 0.49-1.32). For pts with del(17p)/TP53mut, 3-yr PFS in the VO arm was 62.0% (82.7% for pts without del(17p)/TP53mut) compared to 79.4% (81.0%) in the I arm (HR 1.20, 95% CI 0.40-3.59), and 69.0% (80.1%) in the VI arm (compared to I: HR 0.70, 95% CI 0.22-2.16). The most frequent AEs were infections and infestations (VO: 76.3%, VI: 80.2%, I: 79.9%), gastrointestinal disorders (VO: 59.7%, VI: 74.3%, I: 63.4%), and blood and lymphatic system disorders (VO: 59.0%, VI: 42.9%, I: 28.5%). Covid-19 infection was reported in 38.3%, 42.2% and 39.3% of pts; cardiac disorders occurred in 13.9%, 23.8% and 34.6% of pts; second cancers were reported in 11.5%, 11.2% and 18.5% of pts, respectively. Conclusion This is the first phase 3 trial comparing the main paradigms of continuous vs fixed-duration targeted therapy of CLL. Early findings indicate that fixed-duration treatment with VO or VI are non-inferior to continuous treatment with I and may therefore represent the preferred treatment option for pts with previously untreated CLL.

BACKGROUND: Very old and frail patients remain underrepresented in clinical trials, although accounting for roughly 20% of patients with CLL. A higher comorbidity burden and vulnerabilities in this cohort limit the use of results from younger and fit patients. The CLL-Frail trial aims to evaluate the efficacy and safety of acalabrutinib monotherapy in patients ≥80 years of age and/or a FRAIL scale score of ≥3. The FRAIL scale score is a 5-item self-assessment questionnaire for patients correlating with Fried's frailty phenotype (Abrahamian, 2017). We here present the primary endpoint analysis as pre-specified in the protocol. The analysis was performed after all patients had reached the initial response assessment (cycle 7, day 1 = approx. 6 months after initiation of therapy). METHODS: Patients in need of treatment with previously treated and untreated CLL and ≥80 years of age and/or a FRAIL scale score ≥3 were eligible. A maximum of one previous therapy was allowed. Patients received acalabrutinib 100mg BID until progression or intolerance. The primary endpoint was overall response rate (ORR) at the initial response assessment for patients receiving at least 3 cycles of therapy (full analysis set, FAS) with the aim to test the null hypothesis of ORR ≤ 65%. Secondary endpoints included overall survival (OS), progression-free survival (PFS) as well as frequency and severity of adverse events. RESULTS: 53 patients were included into the trial (ITT population), one patient withdrew consent before receiving study medication, and 46 patients completed at least 3 cycles of therapy (FAS). In the ITT population median age was 81 years (range 54-91), 47% had a FRAIL scale score of ≥3. Median CIRS score was 9, with 68% of patients having a score >6. 79% of patients had an ECOG score ≥1. Unmutated IGHV and aberrant TP53 was present in 60% and 23%, respectively. 36 patients (68%) were treatment naïve. In the previously treated cohort, prior lines of treatment included chemoimmunotherapy in 13 patients (76%), while four patients (24%) were treated with targeted therapy. At the data cut on the 15th of January 2024 the median observation time was 17.7 months, 34 patients (65%) remained on therapy. Six patients (12%) discontinued therapy before reaching cycle 4. Reasons for discontinuation in all patients were adverse events in ten (56%), death in five (28%) and withdrawn consent in three (17%) patients, respectively. With 43 of 46 patients achieving a PR at cycle 7 day 1 the ORR in the FAS was 93.5% (95% confidence interval 82.1 - 98.6) meeting the primary endpoint of the trial (p<0.001). One patient had a stable disease and two patients had missing response assessments. There were no progressive diseases. In the ITT population estimated 12-month PFS and OS rates were 87.5% and 91.9%, respectively. The estimated 12-month PFS and OS-rates in frail patients were 90.9% and 90.9%. 53% of FAS-patients had an improvement in their FRAIL scale scores, with 21% of patients considered frail at month 6, compared to 47% at screening, according to self-assessment. All patients experienced at least one AE. Most common AEs were COVID-19 (40% of patients) and hematoma (37%). There were a total of 40 SAEs in 26 (50%) patients. There were no cases of severe (CTC° ≥3) bleeding. Since the interim safety analysis in 2023 there were no further cases of atrial fibrillation, the total remaining at two cases (CTC° 2 and 3). Five patients (9%) died. Causes of death were infection in three cases (one bacterial and two COVID-19 pneumonia) and concomitant disease in one case. There was one deadly SAE termed suspicion of cardiac event, in a case of a 85-year old patient with sudden death at home and known cardiac comorbidities. CONCLUSION: This is the first prospective trial aimed specifically at treatment evaluation in very old and/or frail patients with CLL. High response rates and the substantial improvement of frailty demonstrated a remarkable efficacy of the BTK-inhibitor acalabrutinib in this underrepresented age group.

This research paper aims to provide an overview of evidence-based sequencing of therapies in relapsed/refractory chronic lymphocytic leukemia (CLL) in the era of targeted drugs. In the absence of data from randomized clinical trials comparing novel agents head-to-head, growing evidence suggests that patients with late relapse (> 2 years) after fixed-duration therapies benefit from identical retreatment, whereas a class switch is favorable in those with short-lived remissions or progressive disease on continuous drug intake. Treatment of patients previously exposed to both covalent inhibitors of BTK and BCL2 remains an unmet medical need. Novel drugs, in particular noncovalent BTKI, show promising efficacy in this difficult-to-treat subgroup in early clinical trials. The optimal sequencing of therapies in CLL requires consideration of individual patient factors and disease characteristics. Double-refractory disease continuous to pose a clinical challenge with a focus on participation in clinical trials whenever possible.

Introduction Overall survival (OS) is generally considered the most patient-relevant endpoint in oncology trials, however, its implementation can entail several challenges in the context of chronic lymphocytic leukemia (CLL): 1) The competing survival risk due to comorbidities in the mostly elderly CLL patient population; 2) the high efficacy of targeted therapies warrant longer observation periods or extensive patient recruitment, which can be operationally challenging; 3) the interference with increasingly potent relapse therapies, which can neutralize differences of efficacy of first line regimen. Hence, surrogate endpoints, such as progression-free survival (PFS), overall response or complete response rate (ORR, CR) or minimal residual disease (MRD), are commonly used in CLL research. However, data supporting a correlation between surrogate endpoints and OS in the treatment for CLL is scarce. Here, we present a large, systematic analysis of over 4000 patients (pts) treated in studies of the German CLL Study Group (GCLLSG) to determine the adequacy of surrogate endpoints in clinical trials for pts with CLL. Methods We analysed twelve phase II and phase III trials of the GCLLSG spanning from 1999 to 2022. Only pts receiving first-line therapy were included in the analysis. To determine correlation, the Kaplan-Meier survival function was estimated for both OS and PFS for each study separately. From these functions, the probability of survival (OS and PFS) was estimated at different time points. These pairs of time points were then correlated across the studies, with each pair of probabilities weighted by the number of pts in each corresponding study using Spearman's correlation coefficients. Additionally, we compared OS according to MRD and iwCLL response status at end-of-treatment (for fixed-duration regimens) or end-of-induction-treatment (for MRD-guided treatments) (EO[I]T) using Kaplan-Meier functions calculated from the time point of MRD assessment in peripheral blood. EO(I)T ranged from month 9 to month 15 after treatment initiation, depending on the study protocol. Results The full analysis set comprised 4237 pts. The median observation time was 67 months. Median age was 64 years (range 27 - 90). 45.1% of pts were older than 65 years. 3159 pts (74.6%) had received chemo/chemoimmunotherapy (C/CIT), whereas 1078 (25.4%) were treated with targeted therapies. There were 2114 progressive disease (PD) events and 1211 deaths captured within the trial data. The Spearman's Rho of the estimated survival probabilities for the time points 12/24, 24/36, 36/48 and 60/72 months (PFS/OS) was 0.95, 0.96, 0.94 and 0.92, respectively ( Panel A). Focussing on pts with confirmed OS event (n=1211), the Spearman's Rho between PFS and OS in months was 0.66 for pts receiving chemo/chemoimmunotherapy and 0.88 for pts receiving targeted treatment. ORR and CR rate was 89.8% and 31.5%, respectively. Pts with a CR had a significantly longer PFS (HR 0.38, 95% CI 0.34-0.42, p <0.001) and OS (HR 0.39, 95% CI 0.33- 0.46, p <0.001) compared to pts with non-CR. MRD measurements at the EO(I)T were available for 2521 pts (59.5%), of which 39% were treated with targeted agents. Rates of undetectable (<10 -4), intermediate (≥10 -4 and <10 -2) and high MRD (≥10 -2) were 59.1%, 21.7%, 19.3%, respectively, across treatment groups. The median OS for undetectable and intermediate MRD was not reached and 60.7 months for high MRD status ( Panel B). The estimated 60-month OS was 84.6%, 71.3% and 51.1%, respectively. Accordingly, median PFS for uMRD was 61.8 months and 60-month PFS was 52.6%. In pts ≤65 years of age, median OS was not reached with undetectable or intermediate MRD and 70.5 months in pts with high MRD status. In pts >65 years, median OS was not reached for uMRD and was 75.2 and 58.8 months, respectively, for pts with intermediate or high MRD. The corresponding hazard ratios for high versus uMRD status at EO(I)T were 3.33 (95% CI 2.57 - 4.3) in older and 5.89 (4.15 - 8.35) in younger pts. Conclusion In this large analysis of 12 prospective CLL trials, we found a robust correlation between PFS and OS, thereby supporting the use of PFS as a surrogate endpoint in clinical studies. More importantly, the MRD status at EO(I)T was associated with OS across all treatment modalities, demonstrating its utility in identifying pts with potentially dismal outcomes and providing a rationale for MRD-guided treatment strategies.

Background: The presence of ≥3 (complex karyotype, CKT) and specifically ≥5 (high-CKT, hCKT) chromosomal aberrations (CA) is associated with a poor prognosis in patients (pts) with chronic lymphocytic leukemia (CLL) treated with chemoimmunotherapy (CIT). Studies on the prognostic impact of CKT with targeted agents are not only heterogeneous in size and methodologies but also conflicting, with reports on both negative impact (venetoclax [ven] + rituximab [RVe] and ibrutinib monotherapy) and no impact (ven + obinutuzumab [GVe], ven + ibrutinib, idelalisib + rituximab) on progression-free (PFS) and overall survival (OS). Here, we prospectively evaluate the impact of CKT in a large cohort of pts treated with ven-based time-limited combinations within the GAIA/CLL13 trial. Methods: The phase 3 GAIA/CLL13 trial compared 3 different time-limited ven-based combinations against CIT in fit, treatment-naïve pts with CLL. Pts with TP53 aberrations were excluded. Pts were randomized to CIT (FCR in pts ≤65y; BR in pts >65y), RVe, GVe, or GVe plus ibrutinib (GIVe). Chromosome banding analyses were performed following IL-2/CpG-stimulation, karyotypes were analyzed according to ISCN 2020. No CKT (nCKT) was defined as ≤2, CKT as ≥3, intermediate CKT (iCKT) as 3-4 and hCKT as ≥5 CA. Undetectable MRD (uMRD) was defined as less than 1 CLL cell/10 000 leukocytes measured by 4-color flow cytometry. Results: Chromosome analysis was successfully performed at baseline in 895 of 926 pts. Of these, 672 (RVe: 231; GVe: 218; GIVe: 223) were in the pooled ven population (pooled ven) and 223 in the CIT arm. nCKT was present in 79.4%, 81.0%, 83.5%, and 87.9%, iCKT in 13.5%, 14.7%, 11.5%, 9.4% and hCKT in 7.2%, 4.3%, 5.0% and 2.7% of pts treated with CIT, RVe, GVe and GIVe, respectively. Male gender, del(11q), del(6q) and trisomy 12 were associated with CKT. No correlation was observed between IGHV status or CLL-IPI and CKT. With CIT, uMRD rates in peripheral blood at month 15 were lower in pts with CKT compared with nCKT (37.0% vs 57.1%; OR 0.44, p=0.016). In none of the ven arms, uMRD rates were significantly different between pts with CKT and nCKT (RVe: 52.3% vs 56.7%, GVe: 86.1% vs 86.3%, GIVe: 92.6% vs 92.3%). Across all treatment arms, pts with ≥5 CA had significantly shorter PFS than pts with <5 CA (Figure 1). With CIT, also iCKT was associated with shorter PFS (vs nCKT: HR 2.49, p=0.003), while in none of the ven arms there was a significant PFS difference between iCKT and nCKT (RVe: HR 1.35, p=0.376; GVe: HR 0.94, p=0.912; GIVe: HR 0.38, p=0.341). Pts harboring translocations (TL) (CIT: n=52 [23.4%], pooled ven: n=160 [24.1%]) had inferior PFS compared to pts without TL irrespective of the treatment arm (Figure 2). Focusing on the ven-treated population, this difference was mostly driven by unbalanced TL (vs no TL: HR 3.83, p<0.001) however balanced TL still conferred inferior PFS compared to pts without any TL (HR 1.66, p=0.035). Pts with CKT but without TL had comparable PFS to nCKT (HR 0.53, p=0.217) whereas pts with CKT and TL had significantly shorter PFS (HR 2.79, p<0.001). In pooled ven, particularly pts with TL involving 8q (n=22) or 18q (n=29) showed significantly shorter PFS (HR t(8q;x) 3.94, p<0.001; HR t(18q;x) 2.48, p=0.006), while with CIT numbers were too small for reliable conclusions (n=5 and n=6, respectively). In a multivariate analysis, CKT was identified as an independent prognostic factor for PFS with CIT, while in pooled ven, only hCKT and TL were identified as independent adverse factors for PFS. OS was shorter for CKT vs nCKT with CIT (HR 3.25, p=0.044), but not in the ven arms. At progression (PD), karyotyping data was available in 88 of 161 (54.7%) pts. With CIT, 7 of 20 (35.0%) pts with nCKT at baseline acquired CKT at PD, in the pooled ven group this fraction was substantially smaller (6/45, 13.3%). With CIT, the number of CA increased between baseline and PD (mean, 2.0 to 3.4) while it remained stable after ven (2.1 to 2.0). Conclusions: In pts lacking TP53 aberrations, hCKT (≥5 CA) but not iCKT (3-4 CA) was associated with shorter PFS following treatment with time-limited ven combinations. While this study confirms the adverse impact of CKT with CIT, it identifies hCKT as an adverse prognostic factor in the context of ven-based combination treatment in CLL. Presence of translocations was associated with inferior PFS in all treatment arms. Karyotyping at relapse shows increased genomic complexity after CIT as opposed to ven-based treatments. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal