Abdallah, Nadine

Abstract Background Central nervous system involvement in multiple myeloma (CNS-MM) is a rare but highly aggressive manifestation. Limited data exists regarding its incidence, biology, treatment patterns, and outcomes. A deeper understanding of the features unique to CNS-MM will help inform risk stratification and management strategies. Methods We conducted a retrospective study of CNS-MM patients at our institution between January 2000 and December 2023. We identified 305 MM patients with pathology-proven extramedullary disease (EMD). CNS involvement was defined as the presence of parenchymal (brain or spine) or leptomeningeal involvement by MM. Univariate analysis was performed to compare the clinical characteristics between EMD patients with and without CNS-MM. Results Out of 305 patients with EMD, we identified 22 patients with CNS-MM. Common symptoms prompting evaluation of CNS-MM were headaches (32%), numbness or tingling (32%), weakness (27%), confusion (23%), falls (23%), and visual disturbances (14%). Among these patients, 17 (77%) had detectable disease in cerebrospinal fluid (CSF), 12 (55%) in the brain parenchyma, 4 (18%) in the spinal cord parenchyma and 6 (27%) in the leptomeninges. Of the CNS-MM patients, the median age at diagnosis of MM was 58.3 years and the median time to CNS-MM involvement was 16.2 months, with 3 (14%) patients having CNS involvement at diagnosis. The predictors of CNS-MM development were high-risk cytogenetics (OR 2.9, p=0.04) and presence of additional visceral organ involvement outside of the CNS (OR 3.4, p=0.03). EMD was multifocal in 20 CNS-MM patients (83%) and visceral organ involvement [most commonly lymphadenopathy (27%), solid organ (18%) and pleural fluid (14%)] was present in 14 (64%) of these patients, compared to 54% in EMD patients without CNS-MM. High-risk cytogenetics [del(17p), 1q gain/amplification, t(4;14), t(14;16), t(14;20)] were seen in 16 (73%) patients, most commonly 1q gain or amplification (40%), t(4;14) (23%), and del(17p) (18%). Five (23%) exhibited a double-hit profile. In comparison, 113 (40%) EMD patients without CNS-MM had high risk cytogenetics. The median overall survival (OS) from diagnosis of CNS-MM was 6 months (95%CI:1.26-36) compared to 15.6 months (95%CI: 12-18) from diagnosis of EMD in EMD patients without CNS-MM (p=0.05). Median OS from diagnosis of MM in the CNS-MM cohort was 36 months (95%CI: 22.8-NA) compared to 55.2 months (95%CI: 45.6-68.4) in EMD patients without CNS-MM (P=0.11). When excluding CAR-T or bispecific therapy recipients, median OS from diagnosis of MM for CNS-MM was 22 months versus 48 months in EMD patients without CNS-MM (P=0.02). Overall response rate in our CNS-MM cohort with first treatment for EMD was 32% compared to 48% in EMD patients without CNS-MM (p=0.04). In patients with CNS-MM, median progression-free survival (PFS) from CNS-MM diagnosis was 3.3 months (95%CI: 0.8-12) versus 3.9 months (95%CI: 3-5.1) in EMD patients without CNS involvement (p=0.2). Six (27%) CNS-MM patients received CAR-T; 3 received cilta-cel, 2 received ide-cel and one received a BCMA CAR-T on trial. Bispecific therapy was used in 4 (18%) patients, with 2 receiving Teclistamab and 2 Talquetamab. Three (14%) CNS-MM patients received both CAR-T and bispecific therapy. The median PFS on CAR-T therapy was 10.5 (95%CI: 5.6-NA) months and 12.7 (95%CI: 10.2-NA) months on bispecific therapy. The median OS from diagnosis of CNS-MM for patients who received CAR-T or bispecific therapy was 36 months (95%CI: 14.0-NA), compared to 1.2 months (95%CI: 0-14.4) for those who did not (p=0.002). Six (27%) patients with CNS-MM, all of whom had CSF involvement of disease, received intrathecal therapy; methotrexate in 3, cytarabine in 2, and one receiving both. Two of these patients demonstrated improvement in cerebrospinal fluid findings following intrathecal chemotherapy, in conjunction with other therapies. Patients who received intrathecal chemotherapy had a median OS measured from development of EMD of 10.8 (95%CI: 3.6-NA) months, compared to 15 months (95%CI: 4.8-NA) in those without IT chemotherapy (p=0.59). Conclusion Central nervous system involvement in MM is relatively uncommon and associated with dismal outcomes. High-risk cytogenetics and involvement of other visceral sites are associated with a higher risk of CNS involvement. Intrathecal therapy offers limited value and immune effector therapies represent efficacious options for treatment.

Abstract Background: Social determinants of health (SDOH) are critical drivers of cancer care access and outcomes. In multiple myeloma (MM), access to cellular therapies including autologous stem cell transplantation and CAR-T therapy often depends on formal or informal caregiver support. Traditional SDOH measures (e.g., race, income, or education) are often used as proxies for access to care; however, these measures may overlook individual realities pertaining to cellular therapies where a caregiver is generally required. In response to feedback from a HealthTree Patient Advisory Board questioning the practice of inferring caregiver support, this study evaluated a simple survey question by a large cross-sectional survey. Methods: After development of a dedicated single-question (“What best describes your current caregiving support?”) through iterative feedback from the Patient Advisory Board and MM experts, four key answers were settled on: (1) cohabitation with dedicated caregiver(s) to support care (“family support”); (2) presence of non-cohabiting caregiver(s) to provide dedicated support (“external support”); (3) lack of dedicated caregiver, hence support is arranged when needed (“arrangeable support ”); or (4) lack of dedicated caregiver, hence finding any support is a struggle (“inadequate support”). We deployed this new demographic question from February through July 2025 through HealthTree. Responses were analyzed across SDOH variables using Fisher exact or chi square tests, and random forest classifiers were employed for predictive modeling. Results: Of 1231 respondents, 71% had dedicated caregivers (68%, n=839, with family support, and 3%, n=41, with external support). In contrast, 23% (n=287) of patients routinely arranged support while 5% (n=64) had inadequate support (struggle to find support). The inadequate-support group had significant demographic differences from the sample as a whole: a higher proportion were women (78% vs 56%, p = 0.04), Black (9% vs 4%, p < 0.01), lived >50 miles from their treatment center (17% vs 6%, p < 0.01), and had an annual income <$50,000 (17% vs 6%, p = 0.02). This group had a numerically higher proportion of patients whose employment status was disabled (12% vs 5%, p=0.08) as well. No proportion difference in age (67 ± 9 yr), military status, or severity of diagnosis - precursor disease (17%) v. multiple myeloma (81%). Rates of inadequate support were overall low in patients who lived with only their spouse (1%) or lived with their spouse & children (3%). In contrast, rates of inadequate support were higher (than 5%) in patients who lived alone (21%), divorced (20%), lived with adult children (14%), lived with friends (13%), separated (11%), or widowed (9%) (p < 0.001). However, the arrangeable-support group comprised 12% of patients who lived only with their spouse, 19% of patients who lived with their spouse and children, and 61% of patients who lived with their adult children (p < 0.001). Finally, a random forest classifier failed to identify any individual in the inadequate-support category, suggesting that unmeasured or more complex patterns may underlie this classification. Conclusions: To our knowledge, this is the largest analysis of caregiver support and its relationship with other SDOH in patients with MM to date. Despite the importance of caregiving to transplantation and CAR-T therapy, we found that 5% of patients with MM struggle to find caregiver support; this figure likely underestimates the true prevalence, given potential selection bias among patients who are digitally engaged through the HealthTree platform. Even among patients who lived with their spouses, an additional 10-20% of patients routinely had to arrange caregiving support on a visit-by-visit basis; for patients who lived with their adult children, this proportion was over 60%. The requirement to arrange caregiving support can create time toxicity and financial toxicity for patients, although these factors were not directly queried in our study. Finally, caregiver availability cannot be routinely inferred from traditional SDOH variables. Our data highlight the importance of including caregiver status as a standard demographic question in clinical and research settings. Further interventions are needed to improve caregiver support for vulnerable patients with MM as well as to reduce the duration of caregiver requirements for procedures such as CAR-T therapy.

Abstract Background Measurable residual disease (MRD) negativity post- autologous stem cell transplantation (ASCT) in newly diagnosed multiple myeloma (MM) is associated with favorable outcomes and may overcome the adverse impact of high-risk cytogenetic abnormalities (HRCAs). However, as the definition of high risk evolves and MRD emerges as a key endpoint, understanding its prognostic value within individual HRCAs is critical for treatment guidance. Methods We retrospectively included patients with NDMM that underwent an ASCT between September 19, 2016, and October 19, 2023, and achieved MRD negativity on Day 100 post ASCT. The MRD testing was conducted using multiparameter flow cytometry with a sensitivity of 2x10. HRCAs were defined as del(17p), 1q21+ gain or amplification (1q21+), t(4;14), t(14;16), t(14;20) and del(1p) and rest were considered standard risk (SRCA). Patients were grouped by the number of HRCAs (0, 1, ≥2). An adaptation of the recently proposed International Myeloma Society (IMS)/International Myeloma Working Group (IMWG) classification for high-risk disease (TP53 mutation unavailable) was also used. Progression-free survival (PFS), measured from stem-cell infusion to progression or death, was estimated using Kaplan–Meier methodology and compared using log-rank test. Results We identified 386 patients with MRD negativity post ASCT, of which 381 had cytogenetic data available for analysis. The median follow-up for the study cohort was 47.3 months (95% CI: 43.2-50). The median age at the time of ASCT was 65.7 (25.4-79.2) years and 58.3% patients were males. A total of 49% (n=189) patients had standard-risk cytogenetics, 31.4 % (n=121) harbored 1 HRCA, 15.3% (n=59) patients had two HRCAs and 3.1% (n=12) had 3 HRCAs. The individual HRCA by their prevalence were: 1q21+ in 35.5%(n=137), del(17p) in 14.3% (n=55), t(4;14) in 10.9% (n=42), t(14;16) in 5.4% (n=21), del(1p) in 4.2% (n=16), and t(14;20) in 1.04% (n=4) of patients. The most common double-hit lesions were1q21+ gain and/or amplification co-occurring with t(4;14) (33.9%, n=20) and del(17p) with 1q21+ (18.6%, n=11). Despite universal MRD negativity at Day 100, several HRCAs remained prognostically significant for PFS. Patients with del(17p) had worse 3-year PFS (71%) than those without (81%) [hazard ratio (HR)=1.85, 95% CI 1.11–3.07, p = 0.0172], though 3-year OS did not significantly differ at data cutoff (80% vs. 92%, p=0.1176). Presence of 1q21+ was associated with an inferior 3-year PFS (73%) compared to those without [84%, HR: 1.96 (95% CI: 1.25–3.06), p=0.0026], while 3-year OS was similar (88% vs. 91%, HR:1.33 p=0.36). Isolated 1q21+ had inferior PFS with comparable OS when compared to SRCA [3-year PFS of 82% vs. 88% respectively (HR:1.97, p=0.0177)]; 3-year OS was 91% vs. 94% (HR:1.38, p=0.44)]. Among 1q21+ patients, those with co-occurring HRCAs had a 3-year PFS of 66% vs. 81% for isolated 1q21+ (HR: 1.47, p=0.21). Patients with t(4;14) had worse 3-year PFS (64%) vs. 82% in non t(4;14) [HR 2.11(95% CI: 1.21-3.67) p=0.0064], and 3-year OS of 82% compared to 91% [HR 2.14 (95% CI: 1.02–4.49), p=0.038]. Isolated t(4;14) showed a 3-year PFS of 59% vs. 87% in standard-risk (p=0.06), and 3-year OS of 90% vs. 93% [HR 3.29, 95% CI 0.95–11.33, p = 0.06]. The presence of t(14;16), t(14;20), and del(1p) did not significantly affect 3-year PFS (all p>0.1), likely due to small subsets. When patients were grouped by the number of HRCAs, PFS declined with increasing cytogenetic complexity. Compared to standard risk, the 3-year PFS was 77% for 1 HRCA vs [HR = 2.11 (95% CI: 1.29–3.46), p = 0.0027], 67% for ≥2 HRCA [HR = 2.64 (95% CI: 1.53–4.57), p = 0.0005]. Maintenance therapy was used in 98% of patients. Patients with HRCAs received a doublet maintenance compared to SRCA (p<0.0001), even in MRD negative disease post ASCT. Conclusion In patients with certain HRCA, achievement of MRD negativity post-ASCT does not overcome the adverse impact of HRCA on PFS. In our cohort, patients with del(17p), t(4;14), or 1q21+ continued to exhibit significantly shorter PFS despite achieving MRD-negative status. These findings underscore the need for ongoing risk-adapted strategies even in patients with MM who attain MRD-negative state. The OS estimates are immature at this time.

Abstract Background Primary plasma cell leukemia (pPCL) is a rare and aggressive variant of multiple myeloma (MM), characterized by the presence of more than 5% circulating plasma cells on a peripheral blood smear. Despite advancements in therapy, including novel agents and autologous stem cell transplantation (ASCT), pPCL remains associated with markedly poorer survival outcomes compared to newly diagnosed MM. Although disease progression is common in pPCL, individual courses vary widely upon relapse and thereafter. We aim to describe the natural history of pPCL, focusing on clinical features and survival outcomes at the time of relapse or disease progression. Methods Patients with pPCL who were followed at our institution's cancer center between 2006-2024 were included for retrospective analysis. The electronic health record was reviewed to provide detailed information on patient demographics, disease characteristics, treatment regimens, and clinical outcomes. Time to next treatment (TTNT) and overall survival (OS) analysis were performed using the Kaplan-Meier method. Statistical analyses were performed using the SAS biostatistical software JMP 17.0.1 (SAS Institute Inc). Results We analyzed a cohort of 106 patients with relapsed pPCL after first-line therapy, all of whom received induction with novel agents. To date, 64 patients (60%) have died. Across the entire cohort, median OS is 39 months (mos) (95% CI: 25-68). 59 patients (56%) were diagnosed after 2015. Baseline FISH cytogenetics were available for 100 patients; 57 (57%) had one or more high-risk cytogenetic abnormality. Nearly all patients (96%) had ≥50% clonal plasma cells on initial bone marrow biopsy. While most patients (n = 61; 58%) were planned to undergo upfront ASCT, 20 (33%) experienced disease progression during induction therapy and required a more intensive salvage regimen (often infusional chemotherapy) prior to ASCT. The median TTNT after first-line therapy (TTNT#1) for the entire cohort was 10.4 mos (95% CI: 8–14). The median TTNT after second-line therapy (TTNT#2) for the entire cohort was 5.7 mos (95% CI: 4.3–7.1). Clinical details at first relapse, prompting initiation of second-line therapy, were available for 91 patients. Of these, 26 patients (29%) had symptomatic relapses—due to CRAB features or extramedullary disease—while 65 patients (71%) experienced asymptomatic biochemical progression. Symptomatic relapses were followed by significantly shorter TTNT#2 (3.9 vs. 7.0 mos; p = 0.039) and inferior OS from the start of second-line therapy (7.5 vs. 31.2 mos; p <0.0001) compared to asymptomatic relapses. The median TTNT#2 for patients who relapsed during induction and received salvage ASCT was 6.9 mos (n=20). In contrast, those treated after relapse with non-ASCT regimens (n = 86) fared worse; those receiving novel agent-based combinations, including doublets, triplets, or quadruplets (n=64) had respective median TTNT#2 of 3.3, 6.0, and 3.3 mos. Patients treated with infusional chemotherapy (n = 9) had the poorest outcomes, with a median TTNT#2 of just 1.4 mos. The median TTNT diminished with each subsequent line of therapy: TTNT#3 (n = 73) was 5.8 mos, TTNT#4 (n = 53) was 4.0 mos, and TTNT#5 (n = 35) was 2.6 mos. Patients with pPCL harboring the t(11;14) cytogenetic abnormality who were treated with venetoclax-based regimens (n = 8) during any line of therapy had a longer corresponding median TTNT of 15.0 mos. Additionally, 23 patients received anti-BCMA CAR-T cell therapy as a post-relapse line of therapy. At last follow-up, 15 of these patients (65%) had not relapsed, and after a median 20.7 mos of follow-up, the median TTNT following CAR-T cell therapy had not yet been reached. Patients who received CAR-T after 1-3 prior lines (n=15) had a median TTNT that was not reached; those who had received 4 or more prior lines (n=8) had a median TTNT of 20 mos. ConclusionsDespite the use of novel agent-based combination regimens and ASCT as first-line therapy, most patients with pPCL eventually experience disease progression. Consistent with MM, symptomatic relapse in pPCL is associated with poorer outcomes compared to asymptomatic biochemical progression. Additionally, the duration of response shortens with each successive line of therapy. Notable exceptions include venetoclax-based regimens in patients with t(11;14), and anti-BCMA CAR-T cell therapies: each appear to confer more durable responses than historical treatments in patients with relapsed pPCL.

ABSTRACT Light chain multiple myeloma (LCMM) is a subtype of multiple myeloma (MM) characterized by the exclusive production of immunoglobulin light chains and accounts for 15%–20% of newly diagnosed MM. A comprehensive comparison of LCMM with MM producing intact immunoglobulin (non‐LCMM) remains limited. In this retrospective study, we described distinct clinical and cytogenetic features and assessed long‐term outcomes in 852 LCMM patients diagnosed between 01/01/2004 and 12/31/2022, compared with non‐LCMM controls matched for age, sex, and year of diagnosis. On univariable analysis, LCMM patients were more likely to present with elevated creatinine (> 2 mg/dL), beta‐2‐microglobulin ≥ 5.5 mg/L, elevated LDH, hypercalcemia, t(11;14), del(13q), and t(6;14). Conversely, IMS‐IMWG high‐risk disease, hyperdiploidy, t(4;14), and serum albumin < 3.5 g/dL were less common. On multivariable analysis, elevated creatinine (OR: 5.1, 95% CI: 1.2–27, p = 0.04), t(11;14) (OR: 2.6, 95% CI: 1.3–5.2, p = 0.006), and del(13q) (OR: 4.1, 95% CI: 2.1–8.2, p < 0.001) were independently associated with LCMM, while IMS‐IMWG high‐risk disease (OR: 0.3, 95% CI: 0.1–0.8, p = 0.02) and hyperdiploidy (OR: 0.3, 95% CI: 0.1–0.7, p = 0.002) were less frequent. Despite these differences, progression‐free survival with frontline treatment (HR: 0.97, 95% CI: 0.84–1.11, p = 0.63) and overall survival (HR: 0.99, 95% CI: 0.87–1.13, p = 0.94) were similar between LCMM and non‐LCMM patients. This study highlights the distinct clinical and cytogenetic features of LCMM, marked by higher rates of renal failure, t(11;14), and del(13q), lower prevalence of IMS‐IMWG high‐risk disease, and comparable survival outcomes.

Abstract This retrospective analysis examined 15 years of autologous stem cell transplantation (ASCT) for light chain (AL) amyloidosis at the Mayo Clinic (2010-2024). We aimed to assess ASCT utilization trends, factors influencing practice changes, and current indications amid newer therapies. Four hundred and forty-one ASCTs were divided into cohort 1 (2010-2019) and cohort 2 (2020-2024), revealing a significant ASCT reduction in cohort 2 (385 vs 56, average 71% annual decrease). Cohort 2 patients were older, more likely to have relapsed/refractory disease, and had higher baseline bone marrow plasma cell burden compared to cohort 1. Pre-ASCT induction was more frequent in cohort 2 (89.3% vs 56.4%), with daratumumab (Dara)–cyclophosphamide-bortezomib-dexamethasone (CyBorD) replacing CyBorD as the predominant induction regimen. Lymphoma-based regimens were also more common in cohort 2 (15.1% vs 5.3%, P = .02). Day-100 satisfactory hematological response improved in cohort 2 (91.1% vs 72.7%, P = .001), although hematological complete response rates did not significantly differ (50.9% vs 38.8%, P = .09). In summary, there is a decrease in the utilization of ASCT in AL amyloidosis. This procedure is primarily reserved for patients with suboptimal responses, relapsed/refractory disease, lymphoplasmacytic clones (predominantly immunoglobulin M amyloidosis), or high bone marrow plasma cell burden (myeloma phenotype). This study underscores a significant shift in ASCT practice, driven by novel therapies, emphasizing more personalized management in AL amyloidosis.

e19531 Background: Effective treatment and elimination of clonal plasma cells (PC) in multiple myeloma (MM) are typically associated with recovery of polyclonal (normal) plasma cells (PPC). Studies suggest that robust PPC recovery is associated with better outcomes. However, it is unclear if this remains valid in the context of monoclonal antibodies, such as Daratumumab, that selectively target plasma cells, and in turn, may adversely impact PPC recovery. Methods: We identified patients with MM who underwent MRD testing using Euroflow method at 6-12 months after treatment initiation. Eight patients had disease progression prior to MRD testing and were excluded from further analysis. PPC was quantitated by the proportion of total events acquired during flow examination. Patients were considered MRD-negative if they had <1 clonal PCs in 10 5 cells, as detected in the marrow. We first examined the impact of initial therapy (Daratumumab vs. non-Daratumumab based regimens) and MRD status on PPC recovery. Subsequently, we analyzed impact of PPC recovery on patient outcomes in terms of progression-free survival (PFS) and overall survival (OS). Results: We identified 572 patients who had MRD testing by flow at a median of 9 months (range 6-12) after treatment initiation. The median age was 63 years, 58% were male. Daratumumab was part of initial therapy in 17% of patients; the most common induction therapies were PI-IMiD triplets (73%), and dara-PI-IMiD quads (15%). In our cohort, 74% of patients were MRD-negative. In our practice, only samples with no monotypic PCs identified on initial low-sensitivity flow proceed to MRD testing, hence, the proportion of MRD-negative patients appears higher in our study than previously reported. Median PPC was 0.02% and was similar between MRD-negative and -positive patients. We found the median PPC was significantly low in patients who received Daratumumab compared to the non-Daratumumab treated cohort (0.011% vs. 0.023%; p<0.01). There was a trend towards lower PFS and OS among the lowest PPC quartile group compared to the upper 3 quartiles, although this was not significant (p=0.07 for PFS and OS, Wilcoxon). This trend was more evident among patients who did not receive Daratumumab. Conclusions: Our study demonstrates negative impact of anti-CD38 therapy with Daratumumab on recovery of PPCs after initial treatment, consistent with the persistent hypogammaglobulinemia seen in clinical practice among these patients. However, unlike the observation with the non-Daratumumab treated cohort, the low proportion of PPCs does not significantly impact patient outcomes among patients who received Daratumumab.

e19545 Background: Cytogenetic abnormalities (CA) at diagnosis are important prognostic factors in multiple myeloma (MM), but there is limited information on how these abnormalities evolve at first relapse and their significance. Methods: This retrospective study included patients aged ≥18 years, with a confirmed diagnosis of MM who experienced at least one disease relapse and had fluorescence in situ hybridization analysis within six months of both diagnosis and relapse. Data on CA and clinical outcomes were collected. High-risk (HR) secondary CA were defined as the presence of deletion of chromosome 17p (del17p) or gain or amplification of chromosome 1q. The primary objective was to evaluate changes in HR secondary CA at first relapse, while the secondary objective was to assess the impact of the cytogenetic changes on overall survival (OS) from diagnosis. Based on the presence or absence of HR secondary CA, patients who were tested for HR secondary CA at both time points were classified into four groups: 1) persistent absence of HR secondary CA, 2) emergence of HR secondary CA at relapse, 3) persistent presence of HR secondary CA, and 4) loss of HR secondary CA at relapse. Results: A total of 233 patients diagnosed between 2004 and 2023 were included. HR secondary CA were tested in 98.7% (n= 230) of patients at diagnosis, with 24.8% (n=57) testing positive. At first relapse, testing for HR secondary CA was performed in 97.4% (n=227) of patients, of whom 23.8% (n=54) tested positive. Del17p was evaluated in 98.3% (n=229) of patients at baseline and 95.7% (n=223) at relapse, with positivity increasing from 10.9% (n=25) to 15.3% (n=34). Gain or amplification of chromosome 1q was evaluated in 49.4% (n=115) at baseline and 25.5% (n=60) at relapse, with positivity rate rising from 28.7% (n=33) to 38.3% (n=23). There were no differences in overall response rate or very-good-partial-response-or-better rates to the initial therapy at diagnosis between the groups. (Table) Emergence/persistence of HR CA were associated with lower OS from diagnosis. Conclusions: Emergence of HR secondary CA at first relapse in MM has prognostic significance. These findings highlight the importance of serial cytogenetic testing for risk stratification. Response rate to initial line of therapy and overall survival from diagnosis among patients tested for HR secondary CA both at diagnosis and first relapse (n=224). Outcome Persistent absence of HR secondary CA(n=142) Emergence of HR secondary CA at relapse (n=25) Persistent presence of HR secondary CA (n=27) Loss of HR secondary CA at relapse(n=30) p-value Overall response rate a 75% (106) 76% (19) 63% (17) 67% (20) 0.5 b Very-good-partial response or better response rate 43% (61) 36% (9) 44% (12) 40% (12) >0.9 b Median (95% CI) OS from diagnosis in years 11.3 (9.7-13.4) 7.5 (5.1-12.1) 6.1 (4.2-9.4) 10.1 (6.5-14.1) <0.0001 c a Partial response or better; b Chi-square test; c Log-rank test.