Availability Of Novel Agents Research Articles

Evaluating population-level outcomes in Chronic Lymphocytic leukemia in the era of novel therapies using the SEER registry

In the last decade, novel agents such as BTK and BCL-2 inhibitors have revolutionized treatment of CLL/SLL, with clinical trials showing improved overall survival compared to chemotherapeutic agents. However, studies examining whether they have improved overall survival at the population level are lacking. We evaluated this by conducting a retrospective analysis of CLL/SLL patients registered in the National Cancer Institute’s surveillance epidemiology and end results (SEER) database, analyzing overall survival (OS) in periods pre- and post-availability of novel agents, along with demographic information. Our results showed that median OS significantly improved over time [7.8 years (2000–2005), 9.1 years (2006–2013), and not reached (2014–2018) (p < 0.001)]. Compared to diagnosis in 2014–2018, diagnosis in earlier periods was associated with higher mortality risk (2000–2005-HR 1.32, 95 % CI 1.28–1.37, p < 0.001: 2006–2013-HR 1.09, 95 % CI 1.06–1.13, p < 0.001). Lower mortality risk was seen in patients age < 85 years whereas median household income of <$75000 was associated with higher mortality. Our study provides real-world data suggesting a possible multifactorial contribution to improvement in survival, including availability of novel agents, better monitoring, and supportive care. They also show discrepancies in overall survival for CLL/SLL patients due to socioeconomic status and demographic factors.

Real world data on outcomes of anti-CD38 antibody treated, including triple class refractory, patients with multiple myeloma: a multi-institutional report from the Canadian Myeloma Research Group (CMRG) Database

Multiple myeloma (MM) remains incurable despite the availability of novel agents. This multi-center retrospective cohort study used the Canadian Myeloma Research Group Database to describe real-world outcomes of patients withanti-CD38 monoclonal antibody (mAb) refractory MM subsequently treated with standard of care (SoC) regimens. Patients with triple class refractory (TCR) disease (refractory to a proteasome inhibitor, immunomodulatory drug, and anti-CD38 mAb) were examined as a distinct cohort. Overall, 663 patients had disease progression on anti-CD38 mAb therapy, 466 received further treatment (346 with SoC regimens were included, 120 with investigational agents on clinical trial and were excluded). The median age at initiation of subsequent SoC therapy of 67.9 (range 39.6–89.6) years with a median of 3 prior lines (range 1–9). The median PFS and OS from the start of subsequent therapy was 4.6 (95% CI 4.1–5.6) months and 13.3 (95% CI 10.6–16.6) months, respectively. The median PFS and OS of patients with TCR disease (n = 199) was 4.4 (95% CI 3.6–5.3) months and 10.5 (95% CI 8.5–13.8) months. Our results reinforce that real-world patients with relapsed MM, particularly those with TCR disease, have dismal outcomes. There remains an urgent unmet need for the development of and access to effective therapeutics for these patients.

Exploring Autologous Hematopoietic Stem Cell Transplantation (HSCT) Utilization and HSCT Refusal Trends in Multiple Myeloma Patients: A Comprehensive Examination of NCDB Data from 2004 to 2020

Background: Autologous hematopoietic stem cell transplantation (HSCT) remains standard of care in multiple myeloma (MM) in eligible patients and is proven to improve survival. However, a significant number of patients can decline HSCT as part of their treatment. Understanding the patterns and factors behind HSCT refusal is crucial for optimizing patient care and tailoring effective interventions. Methods: A total of 43,653 patients MM patients recommended for HSCT from 2004 to 2020 were identified via the NCDB, after excluding cases with incomplete values. KM curves compared overall survival (OS) between HSCT and non-HSCT patients, with both groups receiving induction chemotherapy. Factors influencing HSCT refusal were determined using multivariate logistic regression with backward elimination. SAS version 9.4 was used to analyze the data. Results: Among 43,653 patients recommended for HSCT only 1.95% (850 individuals) refused HSCT and 98.05% received HSCT. The patient characteristics are presented in Table 1. As noted in Figure 1, the median OS of MM patients who opted for induction chemotherapy followed by HSCT, had a much higher OS of 124 months, compared to the MM patients who declined HSCT and had chemotherapy alone with a median OS of 95 months. On multivariate logistic regression analysis patients aged 60-69 and those aged 70 and above demonstrated higher odds of refusing HSCT compared to those below 50 years, with OR of 1.50 (p = 0.0120) and 3.26 (p &amp;lt; 0.0001), respectively. Male patients exhibited decreased odds of HSCT refusal compared to females, with an OR of 0.84 (p = 0.0329). Black patients showed a higher likelihood of HSCT refusal than White patients (OR = 1.38, p = 0.0022). Hispanic patients were less likely to refuse HSCT compared to non-Hispanic patients (OR = 0.65, p = 0.0296). Patients without insurance, those covered by Medicaid/other government insurance and Medicare, exhibited increased odds of HSCT refusal compared to private insurance with ORs of 2.23 (p = 0.0066), 1.38 (p = 0.0366) and 1.34 (p = 0.0048), respectively. Moreover, patients with a Charlson-Deyo score of 2 or 3 had a higher likelihood of HSCT refusal compared to those with a score of 0 (OR = 1.48, p = 0.0024). Patients treated at non-academic facilities were more likely to refuse HSCT than those treated at academic facilities (OR = 2.67, p &amp;lt; 0.0001). Furthermore, patients with a median household income less than $38,000 had increased odds of HSCT refusal compared to those earning $63,000 or more (OR = 1.62, p = 0.0002). Patients with incomes in the ranges of $38,000-$47,999 and $48,000-$62,999 also demonstrated higher odds of refusal with ORs of 1.39 (p = 0.0043) and 1.34 (p = 0.0050), respectively. The year of diagnosis exhibited a significant association with the likelihood of HSCT refusal: patients diagnosed in 2004-2007, 2008-2011 and 2012-2015 had lower odds of refusing HSCT compared to those diagnosed in the reference period (2016-2020), with ORs of 0.16 (p &amp;lt; 0.0001), 0.56 (p &amp;lt; 0.0001) and 0.75 (p = 0.0024), respectively. Geographic location significantly influenced HSCT refusal, with the South Atlantic region (SA) as the reference category. Lower odds of refusal were observed in West South Central (OR 0.29, p &amp;lt; 0.0001), Mountain (OR 0.53, p = 0.001), East South Central (OR 0.63, p = 0.025), and East North Central (OR 0.72, p = 0.01) regions. Conclusion: Our analysis of large real-world database shows that the HSCT significantly improves survival in MM and should be recommended for eligible patients. Furthermore, the study shows that the HSCT refusal rate in real-world is low at ~2% but still represents a missed opportunity to provide standard of care with room for improvement. Older patients (age &amp;gt;60), females, Blacks, non-Hispanics, patients with non-private health insurance, higher comorbidities, non-academic facilities, and lower income (&amp;lt;$63,000/yr), were found to be associated with increased odds of declining HSCT. There was also geographic variation across the USA with higher HSCT refusal in the South Atlantic region compared to other regions. In addition, the increasing trend in HSCT refusal from 2004 to 2020 is likely due to advances in MM therapeutics due to the availability of novel agents and anti-CD38-immunotherapy. Our study suggests significant racial, economic, and geographic variation regarding the utilization of HSCT across the US which should be further studied in prospective studies.

Trends in Survival Outcomes for Mantle Cell Lymphoma in the Era of Novel Therapies

Introduction Mantle Cell Lymphoma (MCL) is a rare malignancy, associated with aggressive features and poor outcomes. Previous treatment paradigms for MCL involved chemoimmunotherapy and stem cell transplant (SCT), though this has evolved in recent years with the introduction of novel treatments, including bruton's tyrosine kinase (BTK) inhibitors, chimeric antigen receptor T-cells (CAR-T) and immunomodulatory agents such as lenalidomide. Additionally, the incorporation of rituximab maintenance therapy following SCT has demonstrated improved progression-free (PFS) and overall survivals (OS) for MCL patients (pts). While the majority of these novel agents and treatments were FDA approved by demonstrating improved PFS, the benefits of these new treatments on OS trends for MCL pts are not well described. Therefore, to determine whether these advances have translated to OS improvement in the real-world setting, we performed a national analysis of OS trends through multiple treatment eras. Methods The National Cancer Database was used to identify pts diagnosed with MCL from 2004-2020. For pts receiving treatment, the use of front-line single or multiagent therapy, and upfront SCT was compared. Kaplan-Meier and Cox regression analysis was used to compare OS for all MCL pts. Survival was compared by year of diagnosis, with diagnosis in 2004-2013 considered to be managed in the era of chemoimmunotherapy, 2014 and later associated with the introduction of BTK inhibitors, and 2017 and later with the adoption of maintenance rituximab following SCT. Results A total of 31,284 pts with MCL were identified. The mean age at diagnosis was 67 years (yrs) [SD ±12], 93% of pts were White, and 70% had stage IV disease at diagnosis. Pts were increasingly more likely to have ≥2 comorbidities at MCL diagnosis (6.2% from 2004-2013, 8.6% from 2014-2016, and 10.8% from 2017-2020) and were increasingly managed at academic centers (40%, 44%, and 46%, respectively). Rates of pts managed with active surveillance significantly increased over time (4.7% from 2004-2013, 6.7% from 2014-2016, and 8.7% from 2017-2020). Regarding treatment, the rate of upfront multi-agent chemotherapy use decreased over time (67.7% from 2004-2013, 45.2% from 2014-2016, and 38.9% from 2017-2020), corresponding with an increase in single agent treatment (7.9%, 28.2%, and 32.4%, respectively). Notably, the rate of pts receiving SCT following front-line treatment remained similar in each time period (13.6%, 15.4%, and 14.1%, respectively). With a median follow-up of 3.5 yrs, the median OS for all pts with MCL from 2004-2020 was 5.9 yrs (95% CI 5.8-6.0 yrs). The median OS was significantly increased when comparing pts who were diagnosed between 2004-2013 (5.5 yrs) to those diagnosed 2014-2016 (6.8 yrs), and median was not reached for pts diagnosed 2017-2020 (all p&amp;lt;0.001). The median 1-, 3-, and 5-year OS significantly increased following the availability of novel agents after 2014 (2004-2013: 1-year 80%, 3-year 63%, 5-year 52% vs. 2014-2016: 1-year 82%, 3-year 67%, 5-year 58%, p&amp;lt;0.001). Whereas, pts diagnosed from 2017-2020 had similar OS trends as pts diagnosed from 2014-2016 with 1-year 82%, 3-year 66%, 5-year 51% OS, respectively. When adjusted for age and comorbidity burden, the most recent time periods were associated with decreased risk of death (2014-2016: HR 0.81 [95% CI 0.78-0.85], and 2017-2020: HR 0.82 [95% CI 0.78-0.86]) when compared to 2004-2013 (all p&amp;lt;0.001). Conclusions: To our knowledge, this is the largest retrospective review evaluating treatment trends and OS outcomes in pts with MCL in recent decades. These data show that OS has significantly improved for pts diagnosed in the most recent time periods. We hypothesize this is due to the introduction of novel agents such as BTK inhibitors, which is supported by the increased rate of single agent treatment over time, which may be related to BTK inhibitors supplanting chemoimmunotherapy in the front-line setting. We also found that no additional OS improvement was observed during the time period following the adoption of rituximab maintenance after transplant, which may be due to the limited number of pts receiving SCT through each time period. With more follow-up data, future studies may determine whether treatments such as CAR-T (FDA approved in 2020 with data not included in this cohort) have further improved OS outcomes for this incurable malignancy.

Primary CNS Lymphoma in Latin America: A Grupo De Estudio Latinoamericano De Linfoproliferativos (GELL) Survey in 80 Cancer Centers in Latin America

Introduction: Primary Central Nervous System Lymphoma (PCNSL) is a rare and aggressive subtype of lymphoma, representing 4-6% of extranodal lymphomas. Management of PCNSL involves a multidisciplinary approach which includes neurosurgery, ophthalmology, radiotherapy, autologous stem cell transplantation (ASCT) and the use of novel agents such as BTK-inhibitors, immunomodulatory agents and chimeric antigen receptor T-cell (CAR-T cell) therapy. These strategies can be costly and not readily available in developing countries. GELL, a multinational group for studying lymphoproliferative disorders, conducted a multicenter international survey to investigate the diagnosis, clinical staging and treatment patterns in Latin America (LATAM). Methods: We conducted an on-line survey consisting of 22 questions regarding diagnostic and treatment patterns of PCNSL in LATAM. All invited centers agreed to participate and contributed for the development of the survey. No identifiable patient information was abstracted at any time during the survey. Questions were structured based on 3 pillars: (1) diagnostic approach, including available biopsy procedures, immunohistochemistry markers, ophthalmology evaluation, flow cytometry and molecular testing; (2) first line therapy, including preferred regimens used for both transplant eligible and ineligible patients, and availability of novel agents, and (3) consolidation therapies including ASCT and whole brain radiation therapy (WBRT) Results: A total of 90 surveys were completed from 80 cancer centers in LATAM. Geographical distribution of the participating cancer centers are as followed: Argentina (n=11), Bolivia (n=2), Brazil (n=9), Chile (n=5), Colombia (n=17), Cuba (n=1), Ecuador (n=5), Mexico (n=10), Panama (n=1), Paraguay (n=4), Peru (n=5), Dominican Republic (n=1), Uruguay (n=5) and Venezuela (n=4). Most centers treat up to 5 new cases of PCNSL/year (84%), with only 3 centers treating more than 15 cases/year. Stereotaxic biopsy was the preferred diagnostic procedure in 78%, and complete resection was done in a minority of centers (3%). Cerebrospinal fluid studies were done in 82% and flow cytometry was available in 87% of the centers. Only 65% of centers had access to PET-CT at diagnosis. Interestingly, 80% of the physicians performed bone marrow biopsy at diagnosis, and ophthalmology evaluation was not available in 20% of the centers. Regarding IHC markers, EBV-LEMP was available in 55% and PDL-1 in only 38% of the centers. FISH for Myc/Bcl2 was performed in 32% and molecular testing in only 23% of the centers. The median time for treatment initiation was 0-10 days in 36%, 10-20 days in 37% and &amp;gt;30 days in 26% of the centers. Regarding first line therapy, MATRIX regimen was the preferred regimen for fit transplant eligible patients in 53% of the participants. However, thiotepa was not readily available as per 45% of the survey participants. Methotrexate (MTX) with Cytarabine was the preferred regimen for 36% of participants. Interestingly, serum monitoring of MTX was not available in 27% of the centers. ASCT was the preferred consolidation regimen for transplant eligible patients (78%), and the most used conditioning regimen was BEAM (49%), suggesting an impact of not availability of thiotepa in these centers. For transplant ineligible patients, MTR (27%), MATRIX (22%) and R-MVP (19%) were the preferred regimens, and 32% of survey participants considered WBRT as the preferred consolidation for these patients. Regarding relapsed/refractory (R/R) PCNSL, MTX-based salvage therapy was the preferred regimen in 38%, followed by cytarabine based in 23% and BTK-inhibitor based in 20% of the participants. CAR-T cell therapy was available in only 3 centers. Conclusion: Management of PCNSL is highly variable in LATAM. Access to targeted agents and novel therapies such as CAR-T cell therapy is limited. Moreover, most centers lack basic diagnostic approaches such as serum MTX level monitoring and ophthalmology evaluation. Lack of access to thiotepa was a common issue encountered by most cancer centers in LATAM. The use of thiotepa-containing regimens has demonstrated improved survivals both as consolidation and in the R/R setting. Thus, the absence of such agent in LATAM carries a profound impact on PCNSL outcomes in this area of the world. A retrospective evaluation on PNCSL outcomes is planned by the GELL group to better investigate our results.

Allogeneic Transplant for CLL Richter's Transformation: Single Center Retrospective Analysis

Introduction: Richter transformation (RT) describes the emergence of an aggressive lymphoma in the setting of chronic lymphocytic leukemia (CLL). The prognosis is poor, with a median overall survival (OS) of 10 months. Treatment of RT is still challenging despite the availability of novel agents, and stem cell transplant (SCT) is commonly used as a consolidation strategy. Data on outcomes post-allogeneic-SCT for RT is limited. The OS on these reports' ranges from 41 to 75%. Methods: We conducted a retrospective study of patients diagnosed with RT at our center who underwent allogeneic SCT between 2005 and 2022. We evaluated predictors of outcome using Cox's proportional hazards regression analysis for overall and progression-free survival (PFS) and Fine and Grey regression for disease progression and non-relapse mortality (NRM). Results: 88 patients were identified, 85 had a diffuse large lymphoma histology and 3 Hodgkin's lymphoma. The median age was 61 years (range 25-74), and the majority (n=61, 69%) of patients were in complete response (CR, N=21) or partial response (PR, N=40) pre-SCT. Median follow-up among survivors was 74 months (range: 8-168); all outcomes are reported at 6 years. Overall, OS was 45% (95% CI: 34-56), and PFS 32% (95% CI: 22-43). The cumulative incidence of disease progression was 41% (95% CI: 31-53) and NRM 25% (95% CI: 17-36). In the univariate analysis, response prior to transplant was the most significant predictor of disease progression, OS, and PFS. Patients in CR/PR had a lower rate of disease progression (32% vs. 61%, HR: 0.2, 95% CI 0.2-0.6, p=0.002) and higher OS (59% vs 16%, HR: 0.3, 95% CI 0.2-0.5, p&amp;lt;0.001, Figure) and PFS (44% vs. 6%, HR: 0.2 (0.1-0.4), p&amp;lt;0.001) compared with those advanced (&amp;gt;CR2)or progressive disease. In addition, the presence of deletion 17p (del17p) or TP53 mutation was associated with a higher rate of disease progression (HR=3.1, 95% C 1.3 -7.3, p=0.01), but not with PFS or OS. The use of reduced intensity regimens resulted in favorable OS (HR=0.5, 95% CI 0.3-1.0, p=0.05) as compared to non-myeloablative conditioning. Age, HCT-CI score, donor type, donor-to-recipient gender, cell source, and graft-versus-host disease prophylaxis, or the presence of other cytogenetic abnormalities were not significantly associated with OS, PFS, disease progression, or NRM. There was also no advantage for any outcome when comparing individuals who achieved CR versus PR pre-SCT. The independent predictive value of CR/PR was confirmed in multivariate analysis for OS (HR=0.3, 95% CI 0.2-0.5, p&amp;lt;0.001) and disease progression (HR=0.4, 95% CI: 0.2-0.8, p=0.01), after adjusting for conditioning intensity for OS and deletion 17p (del17p) or TP53 mutation for disease progression. Discussion: In this single center series of patients treated with allogeneic SCT as consolidation for RT, disease status prior to SCT (CR/PR) emerged as a strong independent predictor of outcomes. The influence of tumor burden prior to SCT may be related to disease biology (e.g., patients not in CR/PR may have more aggressive RT) or may be related to decreased graft-versus-lymphoma effect. Based on our findings, we recommend that aggressive control of the disease with the goal of achieving a CR or PR should be attempted before allogeneic stem cell transplantation in patients with Richter transformation.

Real-world registry of patients with unresectable hepatocellular carcinoma: The OREIOS study.

TPS618 Background: A majority of patients with hepatocellular carcinoma (HCC) are diagnosed with unresectable disease due to extensive extrahepatic spread, presence of multifocal tumors, poor hepatic function or tumor location near major intrahepatic vessels. The treatment landscape for unresectable HCC is rapidly evolving with availability of novel agents, mandating evidence-based therapeutic algorithm for optimum clinical outcomes. Integrating newly approved and emerging therapies in this extremely heterogeneous HCC population with coexisting risk factors (performance status, Child-Pugh class, macrovascular invasion or extrahepatic metastases, and alpha-fetoprotein levels) may pose challenge without understanding survival outcomes with the current treatment practices. Also, application of immunotherapy and targeted agents in clinical practice displays significant regional variations. Real-world evidence on the management of unresectable HCC is sparse across different geographies. The OREIOS study aims to describe the management patterns, clinical characteristics, possible predictors, and survival outcomes in patients with unresectable HCC in 12 countries across Asia, Latin America and the Middle East. The data may serve in devising policies on optimal patient selection and sequencing of novel systemic therapies for unresectable HCC. Methods: OREIOS is an ongoing multicenter, retrospective, non-interventional registry in adults diagnosed between 01 January 2017 and 31 December 2019 with unresectable BCLC stage B HCC, ineligible for initial loco-regional therapy or stage C advanced or metastatic disease, with at least 12 months (or until death if it occurs within 12 months of diagnosis) of available records. Patients with BCLC stage D and other concomitant metastatic cancers are excluded. Data collection includes socio-demographics, clinico-pathological characteristics, treatment modalities, survival outcomes, comorbidities and liver function status. Primary outcome measures include median overall survival using the Kaplan–Meier method and survival rates at 6, 12, 18 and 24 months. Secondary outcomes include clinico-demographic characteristics, treatment regimens (alone or combination) in each line of therapy and real-world progression-free survival. Additionally, prognostic and predictive factors for survival outcomes will be evaluated. Of the planned sample size of 1440 patients, a total of 473 patients with unresectable HCC have been enrolled until August 2022 across 7 countries (Egypt: 105, Hong Kong: 107, India: 79, Russia: 100, Saudi Arabia: 27, Singapore: 50, South Korea: 05). Data collection is currently ongoing and results are expected by 2024. Clinical trial information: NCT05239507 .

Acute myeloid leukemia: challenges for diagnosis and treatment in Latin America

ABSTRACTObjectiveto review the current diagnostic and therapeutic landscape of AML in Latin America as a reflection of other low- and middle-income countries and regions of the world. Encompassing both acute promyelocytic and non-promyelocytic disease types.MethodsWe reviewed the literature and study registries concerning epidemiological features of patients with AML/APL treated in Latin America, as well as evaluated diagnostic and genetic stratification and patient fitness assessment challenges, the importance of early mortality and supportive care capacity, intensive and non-intensive chemotherapy alternatives, consolidation, and maintenance strategies including novel agents and hematopoietic stem cell transplantation.ResultsAlthough most of the current technologies and treatment options are available in the region, a significant fraction of patients have only limited access to them. In addition, mortality in the first weeks from diagnosis is higher in the region compared to developed countries.ConclusionsDisparities in access to technologies, supportive care capacity, and availability of novel agents and HSCT hinder results in our region, reflecting barriers common to other LMICs. Recent developments in the diagnosis and treatment of this disease must be implemented through education, collaborative clinical research, and advocacy to improve outcomes.

Investigating Differences in Treatment (Tx) Patterns and Clinical Characteristics Among Patients (Pts) Diagnosed with Multiple Myeloma (MM) Across Racial Groups

Introduction: Published studies have shown significant racial disparities in MM incidence, Tx patterns, and outcomes. Black/African American (AA) pts have both higher MM incidence and corresponding mortality than White (W) pts. AA pts present at younger median age yet are less likely to be enrolled in clinical trials of novel therapeutic agents or undergo stem cell transplant (SCT). However, in studies performed in equal access situations, AA have comparable or better overall survival, highlighting the importance of improved access to healthcare. Using a large, real-world database we explored how tx patterns and clinical characteristics differ between racial groups and have evolved over a 10-y period. Methods: This retrospective observational study examined MM pts identified in the Flatiron Health from 1 Jan 2011 to 31 Jan 2022. This US-based real-world database collects electronic health records data from community practices (~80%) and academic centers (~20%). Pts aged ≥ 18 y, with a documented MM diagnosis (first diagnosis = index date) between 1 Jan 2011 and 31 Oct 2021 who received at least first-line (1L) systemic therapy and had ≥ 3 mo of follow-up were included. Descriptive statistics were used for all continuous, categorical, and binary study variables. Results: A total of 9083 pts were analyzed: 65% (n = 5904) were W; 20% (n = 1810) were AA; 15% (n = 1369) were 'Other race' (O). These proportions did not vary by year of diagnosis. Before 2015, 33% (n = 3036) of all pts were diagnosed with MM, 52% (n = 4700) diagnosed by 2015-2019, and 15% (n = 1347) diagnosed ≥ 2020. Median age at index was 70, 66, and 68 y in W, AA, and O pts, respectively. A Charlson Comorbidity Index (CCI) score ≥ 1 at index was reported in 9.3% of pts overall; the proportion of pts with CCI ≥ 1 increased over time: W 4.8% (< 2015), 10.2% (2015-2019), and 14.2% (≥ 2020); AA 5.3% (< 2015), 12.4% (2015-2019), and 16.7% (≥ 2020); and O 4.7% (< 2015), 11.3% (2015-2019), and 10.3% (≥ 2020). At diagnosis hypercalcemia was rare (4.2% overall), without appreciable differences by race. Renal insufficiency (creatinine clearance > 2 µmol/L) was seen in 15.9% of pts overall and differed by race: W 15.1%, AA 19.2%, and O 15.2%; this was stable across study periods. Overall 37.9% of pts had anemia; W 35.5%, AA 44.9%, and O 39.8%. Bone lesions, identified using International Classification of Diseases codes, were rare (1.1% overall). Overall, 30.4% of pts received SCT and median time from index date to SCT was 8 mo (232 d). Across race cohorts, 31.8%, 28.7%, and 26.8% of W, AA, and O pts, respectively, received SCT and median time to SCT was 7.4, 8.4, and 8.0 mo for W, AA, and O pts, respectively. The proportion of pts who had triplet or quadruplet 1L regimens was similar across race cohorts (W 58.1%; AA 58.0%; and O 60.3%). While the percentage of pts receiving triplet or quadruplet regimens increased over time for all races and were similar, W pts generally received quadruplet therapy more often than AA and O pts (Figure 1). Before 2015, the most common 1L regimen was lenalidomide + dexamethasone (Rd) across all races (W 23.8%; AA 26.2%; and O 19.4%), and Rd + bortezomib was the most common 1L regimen from 2015 to Jan 31, 2022. The average time from index date to start of 1L therapy was 153, 173, and 170 d for W, AA, and O pts, respectively, indicating a longer time to tx for AA and O pts. Time from diagnosis to 1L tx shortened over time for all races. In ≥ 2020 the percentages of pts treated within 1 mo of diagnosis were W 45.7%; AA 43.0%; and O 49.1% (Figure 2). Average duration of 1L therapy was 13, 13, and 12 mo for W, AA, and O pts, respectively. Conclusion: This real-world study presents pt characteristics and tx patterns using the Flatiron database. Compared with W pts, AA pts were more likely to present with anemia and renal insufficiency, and experienced higher CCI scores over time, possibly indicating later diagnosis. By including pts who received at least 1L therapy, this group of pts analyzed likely represents an equal access setting, despite lower rates of private insurance and delayed tx onset among AA. Thus, in contrast to prior studies, AA and W pts were found to have similar tx patterns, including access to highly active combination therapy and SCT use. This indicates that prior disparities in the availability of novel agents can be overcome with appropriate resourcing, and although limited differences in tx were identified by race, further analysis exploring disparities in access to 1L therapy are needed. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Revising the Treatment Pathways in Lymphoma: New Standards of Care-How Do We Choose?

Diffuse large B-cell lymphoma and follicular lymphoma are the most commonly encountered non-Hodgkin lymphomas in clinical practice. Both are biologically heterogeneous, with management strategies that are becoming increasingly complex. Diffuse large B-cell lymphoma typically exhibits aggressive behavior but can be cured in the majority of cases with immunochemotherapy. While R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) has been the standard of care for decades, the recent combination of polatuzumab-vedotin-R-CHP (rituximab plus cyclophosphamide, doxorubicin, and prednisone) has demonstrated improved progression-free survival for patients with intermediate- and intermediate-high-risk disease. Numerous novel therapies, including targeted agents and immunotherapy-based approaches, have recently been approved for relapsed/refractory disease and have led to improved outcomes. Follicular lymphoma is an indolent lymphoma that remains incurable with standard approaches. Overall survival in most patients is excellent, although a proportion of patients will have early relapsing disease and poorer outcomes. The availability of novel agents in the relapsed/refractory setting has shifted the treatment algorithm, which requires thoughtful consideration of sequencing. This article will review recent developments in the treatment of diffuse large B-cell lymphoma and relapsed/refractory follicular lymphoma.

Long-Term Outcomes of Allogeneic Hematopoietic Cell Transplantation in Patients with Newly Diagnosed Multiple Myeloma

Despite remarkable progress in survival with the availability of novel agents, an overwhelming majority of patients with multiple myeloma (MM) have disease that relapses. Allogeneic (allo-) hematopoietic cell transplantation (HCT) is a potentially curative option for a subgroup of patients with high-risk MM. This study assessed the long-term outcome of MM patients who underwent allo-HCT while in first remission as consolidation treatment. Thirty-three patients with newly diagnosed MM who underwent allo-HCT as part of consolidation therapy between 1994 and 2016 were reviewed retrospectively. Of these patients, 70% underwent autologous HCT before allo-HCT. All patients were chemosensitive and achieved at least partial response before proceeding to allo-HCT. Most received nonmyeloablative/reduced-intensity conditioning (88%) and a matched sibling donor graft (85%). Acute graft-versus-host disease (GVHD) and chronic GVHD occurred in 30% and 61% of patients, respectively. The median duration of follow-up was 64.1 months (range, 1.4 to 199.2 months) for all patients and 164.4 months (range, 56.0 to 199.2 months) for survivors. The median progression-free survival (PFS) was 36 months (95% confidence interval (CI), 8.6 to 73.0 months). The median time from treatment to progression was 73.0 months (95% CI, 30.6 months to not reached). The median overall survival (OS) was 131.9 months (95% CI, 38.4 months to not reached). Of all patients, 39% were alive for more than 10 years, with 46% (n = 6) without progression or relapse. The cumulative incidence of relapse was 18% at 1 year, 39% at 5 years, and 46% at 10 years post-allo-HCT. The cumulative incidence of nonrelapse mortality was 3% at 100 days, 18% at 1 year, 21% at 3 years, and 24% at 5 year post-allo-HCT. On multivariable analysis, high-risk cytogenetics were associated with a shorter PFS (hazard ratio [HR], 2.7; 95% CI, 1.01 to 7.21;P = .047) and OS (HR, 4.91; 95% CI, 1.48 to 16.27;P = .009). Achieving complete remission after allo-HCT also was associated with longer PFS (HR, 0.24; 95% CI, 0.09 to 0.64; P = .004) and OS (HR, .23; 95% CI, .07 to .72; P = .012). Allo-HCT may confer a survival advantage in a selected population of MM patients when performed early in the disease course; additional data on identifying the patients who will benefit the most are needed.

Multicenter comparison of first salvage chemotherapy versus novel therapy regimens in adult relapsed/refractory acute lymphoblastic leukemia

Patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL) represent a heterogeneous population and therefore there is no standard of care first salvage regimen. We conducted a multicenter, retrospective analysis to compare chemotherapy (e.g. HyperCVAD, MOAD, Larson/CALGB-9511, etc.) to novel agents (blinatumomab or inotuzumab) in first salvage. The primary endpoint, overall survival (OS), was not significantly different among treatment arms, with a median OS of 10.6 months with chemotherapy and 10.1 months with novel therapy (p = .799). Similarly, there was no difference in the CR/CRi rate, with a CR/CRi in 18 patients (41.9%) versus 16 patients (47.1%) treated with salvage chemotherapy and novel therapy, respectively (p = .817). Age significantly impacted the probability of achieving CR/CRi with novel therapy versus chemotherapy. This analysis suggests the use of chemotherapy in first salvage still represents an appropriate treatment option, particularly for young fit patients, as the median OS was roughly 10 months regardless of whether patients received novel therapy or chemotherapy in first salvage. For the reported outcomes, 100% of patients in the novel therapy arm received a novel therapy (per design), whereas only 60.5% of patients in the chemotherapy arm required a novel therapy. Thus, 40% of patients did not require a novel therapy for similar OS. This analysis demonstrates that first-line chemotherapy can achieve similar results to novel therapies, especially now that novel therapies are available for subsequent relapses. However, this study has several limitations including younger age, increased CNS involvement, and higher blast percentage in the chemotherapy arm and potential confounders, including selection of treatment sequence as 43 patients (55.8%) ultimately received both chemotherapy and novel therapy. Therefore, a larger, prospective, randomized study with adequate chemotherapy comparators and availability of novel agents upon relapse is warranted to confirm these results.

Efficacy and Safety of Daratumumab with Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma and Severe Renal Impairment or on Dialysis: Final Analysis of the Phase 2 Dare Study

Efficacy and Safety of Daratumumab with Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma and Severe Renal Impairment or on Dialysis: Final Analysis of the Phase 2 Dare Study

Real-World Treatment Patterns, Adherence and Healthcare Resource Utilization for Chronic Lymphocytic Leukemia/Small Lymphocytic Leukemia Among Veterans in the United States

Introduction: Chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) are the most common types of leukemia in adults in the United States. The US veteran population, predominantly older males, are at high risk for CLL/SLL, especially with prior exposure to Agent Orange or other herbicides during military service. With the increasing availability of novel agents and associated improved survival, there is a need to assess the real-world evidence of CLL/SLL burden in US veterans, as well as the clinical and economic outcomes associated with current treatments. The objective of this retrospective cohort study was to examine the clinical burden, costs and healthcare resource utilization of CLL/SLL in veterans.Methods: Adults who were newly diagnosed with CLL/SLL were identified in the Veteran Health Administration dataset from October 2014 to September 2019. Eligible patients were required to have at least 2 visits with CLL/SLL diagnosis, and continuous enrollment of 6 months pre- and 3 months post-index date, defined by the first diagnosis date. The study population was further required to have at least 1 CLL/SLL treatment on or after the index date. Treatment regimens were identified by line of therapy and categorized mutually exclusively as: bendamustine-based (alone or in combination) therapy, other chemotherapies, ibrutinib, rituximab-monotherapy, or other regimen. Descriptive analyses were conducted to examine patient sociodemographic characteristics, comorbidities, concurrent medications, and treatment patterns including the frequency and duration of each treatment regimen. Adherence was measured by discontinuation and switching rates. Discontinuation was defined as no treatment for 90 days from the last day of supply during the study period. To ensure only patients who prematurely discontinued chemotherapy treatment and not those who completed their treatment cycles are captured, premature discontinuation was defined as a treatment duration of <90 days for bendamustine-based and <120 days for rituximab monotherapy. Costs and healthcare resource utilization were examined by first-, second-, and third-line therapy. Healthcare resource utilization examined included hospitalization and length-of-stay (LOS). Total costs were reported for all-cause and CLL/SLL-related, and calculated as the sum of inpatient, outpatient and pharmacy costs per-patient-per-month (PPPM). Multivariable logistic regression was conducted to examine factors associated with costs, frequency and LOS of hospitalizations.Results: Among the 13,664 veteran patients diagnosed with CLL/SLL, 79% were in watch-and-wait and the final study population consisted of 2,861 patients who received at least 1 line of CLL/SLL therapy (mean duration=465 days). Most patients were elderly (median age =70 years), white (83%), and male (98%). Approximately 39% of veterans had concurrent use of proton pump inhibitors at baseline. Average time to treatment initiation from diagnosis to first-line therapy was 315 days. A total of 770 (26.9%) patients further received second-line therapy (mean duration of treatment=318 days) and 199 (7.0%) patients received third-line therapy (mean duration of treatment=229 days). Ibrutinib was the most common treatment regimen across all lines of therapy (first-line: 39%; second-line: 55%; third-line: 43%) with discontinuation rates at 59.6%, 60.1%, and 55.2% in first-, second-, third-line therapy respectively (Figure 1 and 2). The CLL/SLL-related hospitalization rate was 39% with an average LOS of 7 days. Total PPPM all-cause and CLL/SLL-related costs were $26,709 and $17,233, respectively; these costs were increased by line of therapy. Controlling for patient clinical and demographic covariates, treatment discontinuation and treatment switching were statistically significant predictors of higher inpatient admissions, LOS of hospitalizations, and costs.Conclusions: This real-world data demonstrated significant clinical and economic burden associated with CLL/SLL among the US veterans. Furthermore, the suboptimal adherence, as reported by high treatment discontinuation rates and its impact on increasing costs and healthcare resource use, highlights the real-world unmet needs of CLL/SLL management in the veteran population. Future studies are needed to further understand the long-term outcomes of each treatment regimen. [Display omitted] DisclosuresYang: BeiGene, Ltd.: Current Employment. Liu: BeiGene, Ltd.: Current Employment. Tang: BeiGene, Ltd.: Current Employment. Chanan-Khan: Ascentage: Research Funding; Alpha2 Pharmaceuticals: Patents & Royalties: Tabi; Ascentage, Starton, Cellectar, NonoDev, Alpha2 Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; BeiGene, Jansen, Ascentage: Honoraria; Cellectar: Current equity holder in publicly-traded company; Alpha2 Pharmaceuticals, NonoDev, Starton: Current holder of stock options in a privately-held company; BieGene, Jansen, Ascentage: Consultancy.

Response Adaptive Salvage Treatment with Carfilzomib-Thalidomide-Dexamethasone for Newly Diagnosed Transplant Eligible Multiple Myeloma Patients Failing Front-Line Bortezomib-Based Induction Therapy - Final Analysis from the Australasian Leukemia and Lymphoma Group (ALLG) MM17 Trial

Response Adaptive Salvage Treatment with Carfilzomib-Thalidomide-Dexamethasone for Newly Diagnosed Transplant Eligible Multiple Myeloma Patients Failing Front-Line Bortezomib-Based Induction Therapy - Final Analysis from the Australasian Leukemia and Lymphoma Group (ALLG) MM17 Trial

Treatment Patterns and Outcomes in Lenalidomide-Exposed Multiple Myeloma Patients in Real-World Settings: A Multi-Center Retrospective Study

BackgroundTreatment of multiple myeloma (MM) has changed significantly in recent years with the availability of novel agents including monoclonal antibodies (mAbs), proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs) such as lenalidomide. Despite lenalidomide becoming a standard of care across all lines of myeloma therapy, the population of MM patients refractory to lenalidomide and their real-world clinical management has been poorly studied so far, especially outside the reality of interventional clinical trials (Moreau et. al. Blood Cancer J. 2019).With these considerations in mind, we have performed a retrospective study using two databases to better understand treatment patterns and outcomes of MM patients who were treated with lenalidomide and subsequently became refractory to it. This builds on work previously conducted at other data sources (Willenbacher et. al. EHA Library 2020).AimsThe objective of this study was to describe the treatment patterns and outcomes of MM patients exposed to lenalidomide, with a focus on refractory patients, as defined by IMWG (International Myeloma Working Group) consensus, in a real-world clinical setting.MethodsThe study utilised databases from two participating members of the IQVIA MM real world evidence network: University Hospital Frankfurt (Frankfurt) (Germany) and Portuguese Oncology Institute of Porto (IPO-Porto) (Portugal). Since the native format of databases from participating sites differs, key concepts were harmonised based on pre-agreed definitions. The study population included patients with an initial diagnosis of MM between 01/01/2012 and 31/12/2018 based on the IMWG criteria, were 18 years old or older at the time of diagnosis and received two or more cycles of lenalidomide treatment, alone or in combination, at any dose, excluding patients who only received lenalidomide as maintenance therapy. Patients were defined as refractory to lenalidomide treatment if they progressed on treatment or within 60 days following the end of lenalidomide treatment (excluding maintenance setting).Kaplan-Meier curves were produced to evaluate the time to next treatment (TTNT) and overall survival (OS) for lenalidomide exposed and lenalidomide refractory patients. TTNT was defined as the time between the start date of the line of lenalidomide therapy and the start date of the next line of therapy (LoT) or death due to any cause. OS was defined as the time between the start date of the line of lenalidomide therapy and death due to any cause.ResultsThe cohort included 55 and 42 MM lenalidomide-exposed patients from Germany and Portugal respectively. In Germany, 80% were initially exposed to the lenalidomide in LoT 1, whilst in Portugal 71% received initial lenalidomide treatment in LoT 3.In Portugal, following lenalidomide refractoriness, the majority (78%) of patients received chemotherapy and steroids only whilst in Germany a range of treatment types was observed (mAb-based 33%; PI-based 11%; PI/IMiD combo 11%; mAb/IMiD combo 11%; chemotherapy and steroids only 11%; other 22%).The median OS in months for lenalidomide-exposed refractory patients was 7 in Portugal and 31 in Germany; the median OS for non-refractory patients was 40 in Portugal and was not reached in Germany.The median TTNT in months for lenalidomide-exposed refractory patients was 4 in Portugal and 15 in Germany; the median TTNT for non-refractory patients was 14 in Portugal and 53 in Germany.ConclusionThe analysis of real-world data across two countries, showed heterogeneity in lenalidomide treatment patterns, with first exposure typically occurring in LoT 1 or 3. This has led to differences in the calculated TTNT and OS, and as such the results between the two countries cannot be directly compared. The OS from diagnosis for this cohort is being assessed and will provide an insight on the impact of different treatment pathways.Patients who became refractory to lenalidomide moved on to their next treatment much quicker after exposure vs patients who were not refractory to lenalidomide; similarly, patients who became refractory to lenalidomide had shorter OS than patients who were not refractory.Patients typically became refractory early in their treatment journey, indicating a growing population with unmet medical needs. [Display omitted] DisclosuresMetzler: GSK: Consultancy; Takeda: Consultancy; Janssen: Consultancy; AstraZeneca: Consultancy; Amgen: Consultancy; BMS: Consultancy; Sanofi: Consultancy; Pfizer: Consultancy.

New Pathways and New Targets in PTCL

Despite the increasing availability of novel agents over the past decade, and improved understanding of peripheral T-cell lymphoma (PTCL) ontogeny, outcomes for most PTCL patients remain dismal. Improved understanding of their genetic landscape and the identification of novel therapeutic vulnerabilities has certainly expanded the arsenal of targeted agents, many of which are currently under investigation. Nonetheless, the rarity of these lymphomas continues to frustrate efforts to translate these advances in a manner that is clinically impactful, and this challenge is only compounded by their sheer molecular and genetic heterogeneity.

Evolving Treatment Patterns of Healthcare Providers (HCPs) and Multiple Myeloma (MM) Experts from 2013-2017: Analysis of an Annually Updated Online Treatment Decision Tool

BackgroundExpanding availability of novel agents for treating MM has transformed management strategies, particularly for relapsed/refractory (R/R) disease. Since 2013, experienced MM physicians from leading academic institutions and cancer centers (experts) have annually updated an online tool designed to provide HCPs with treatment recommendations for specific patient cases. Previous reports from our tool analyses have shown yearly changes in treatment patterns among experts but a multiyear delay by HCPs in the adoption of many expert-recommended treatment strategies into their practice.MethodsTo develop the tool, 5 MM experts provided treatment recommendations for hundreds of case scenarios across induction, maintenance, and R/R disease settings. To use the tool, HCPs seeking treatment consultation entered patient and disease factors with a planned treatment for that specific patient using dropdown menus and received 5 expert recommendations for their case. HCPs were asked to indicate the impact of expert recommendations on their planned treatment. This report includes analysis and comparison of intended treatment of HCPs for 790 cases entered into the 2017 iteration of tool with expert recommendations for those patient cases. Treatment trends observed in 2017 will also be compared with those from previous years.ResultsConsensus (≥ 3 of 5 experts choosing the same treatment) among experts has been increasing for induction therapy since 2013. In ASCT-eligible patients, regardless of any other factors, experts recommended bortezomib/lenalidomide/dexamethasone (VRd) in 75% of tool cases in 2017, up from 58% in 2016 and 45% in 2013 and 2014. By comparison, HCPs used VRd for 44% of ASCT-eligible patient cases in 2017 and only 19% in 2016. Expert recommendation of VRd for 66% (vs 48% of HCPs) of ASCT-ineligible cases in 2017 also increased from 38% (vs 18% of HCPs) in 2016. Expert recommendations for induction therapy changed most for cases with varying comorbidities, and data from the 2017 tool are shown in the figure below. In patients without specific comorbidities or with cardiac dysfunction only, experts recommended VRd for 87% to 90% of these cases (vs 41% to 44% of HCPs). In cases involving peripheral neuropathy, experts recommended carfilzomib/lenalidomide/dexamethasone (KRd) for 60% and VRd for 30% compared with HCPs selecting KRd for 10% and VRd for 71% of those cases.In the R/R setting, the novelty and broad range of available regimens are reflected in the lack of consensus in treatment recommendations by both the experts as well as the planned treatment of HCPs. In 304 R/R case scenarios, only 36 cases (12%) had an exact expert treatment consensus and 63 cases (21%) had 2 pairs of experts agreeing on the same treatment recommendations. However, overall treatment strategies were similar among experts, with use of triplet regimens including novel agents increasing in 2017. Experts recommended Kd or daratumumab monotherapy for 40% of cases refractory to lenalidomide in 2016. In 2017, experts no longer recommended monotherapy or doublet therapy for R/R cases in this setting. In 2017, the experts recommended triplet regimen therapy for 87% to 97% of cases involving bortezomib-refractory or lenalidomide/bortezomib-refractory patients, and each of the recommendations included either carfilzomib, ixazomib, daratumumab, or elotuzumab compared with only 55% to 60% of their recommendations including triplet therapy with one of these agents in 2016. Again, variation was observed in the intended treatment of HCPs compared with the expert recommendations for R/R cases. In 2017, the intended treatment of HCPs did not match any of the experts' recommendations for 45% of the R/R cases entered into the tool.ConclusionsAnalysis of cases entered into our expert-developed treatment decision tool shows that a wide gap remains between expert treatment recommendations and the intended treatment plans of HCPs for many of the same MM case scenarios. Experts had nearly full consensus on choice of induction therapy; however, differences between expert recommendations in R/R MM are due to availability of multiple triplet-based treatment options in this setting. In addition, newly approved therapies continue to have a strong impact on experts' recommendations as they quickly integrate new agents into their treatment approaches. A detailed analysis of expert and HCP MM practice trends will be presented. [Display omitted] DisclosuresKumar:Celgene, Millennium, BMS, Onyx, Janssen, Noxxon, AbbVie, Amgen, Merck, Oncopeptides, Skyline Diagnostics, Takeda: Consultancy; Skyline: Honoraria; Celgene, Millennium/Takeda, Onyx, AbbVie, Janssen, Sanofi, Novartis, Amgen, Genentech, Merck, Oncopeptides, Roche, Skyline Diagnostics: Research Funding. Lentzsch:Caelum Biosciences: Other: leadership position and stock; BMS: Consultancy; Amgen: Consultancy. Anderson:Gilead Sciences: Membership on an entity's Board of Directors or advisory committees; Oncopep: Other: scientific founder; C4 Therapeutics: Other: scientific founder; Millenium Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; MedImmune: Membership on an entity's Board of Directors or advisory committees.

Real World Outcomes of Newly Diagnosed High-Risk Multiple Myeloma Patients Treated at Princess Margaret Cancer Centre: A Retrospective Chart Review

Background: In the era prior to the availability of novel agents, we have previously reported that the median progression-free survival (PFS) and overall survival (OS) of high-risk (HR) multiple myeloma (MM) patients (pts) undergoing a single autologous stem cell transplant (ASCT) was only 9.9 and 18.3 months, respectively (Chang H et al., Bone Marrow Transplant, 36 (2005), 793). The current study expands our experience in newly diagnosed HR pts and focuses on the outcomes in pts treated with single or tandem ASCT.Methods: A retrospective chart review of myeloma pts was conducted based on pt information retrieved from the Princess Margaret Myeloma Database. 245 pts with HR MM diagnosed and treated in our centre from Oct 1998 to Dec 2016 were identified. Survival rates were calculated using the Kaplan-Meier product-limit method and the log rank-statistic was used for comparison of survival curves.Results: Pts were considered HR based on the presence of any one of the cytogenetic features: t(4:14) (71%), t(14:16) (36%), and chromosome 17p deletion (42%). Characteristics at the time of MM diagnosis of the 245 pts identified as HR are summarized in Table 1. The median age was 60.9 years. First-line therapy included the following: tandem ASCT in 86 pts (35%), single ASCT in 84 pts (34%), and no ASCT in 75 pts (31%). Of the 170 pts who underwent single or tandem ASCT, 119 (70%) received maintenance therapy post-ASCT, including 84% of the tandem ASCT pts and 56% of the single ASCT pts.Median follow-up was 29.3 months (range 1.1-123.7). The median PFS from date of diagnosis of all HR pts was 33.1 months [95% CI 29.3-37.0 months], while the median OS was 79.2 months [95% CI 58.3-90.9 months]. Both PFS (p= 0.0003) and OS (p= 0.0011) were significantly affected by first-line therapy with a median PFS of 53.1 vs 32.9 vs 21.8 months and median OS of 88.5 vs 71.9 vs 55.0 months in pts treated with tandem ASCT, single ASCT and no ASCT, respectively. Tandem ASCT pts had improved PFS and OS survival at 1, 2, and 5-years compared to single and non-transplant pts (Fig. 1A & B). Age at diagnosis significantly affected the PFS (p= 0.0003) and marginally affected the OS (p= 0.0748), likely due in part to our policy for the preferential use of fixed-duration non-ASCT as first-line therapy in older individuals (typically ≥70 years of age). On the other hand, serum beta 2- microglobulin levels correlated significantly with OS (p= 0.0023) while the association with PFS was not significant. Among ASCT pts, those who received tandem ASCTs vs single ASCT demonstrated a significantly better PFS (p= 0.0039) and showed a trend for improved OS (p= 0.0707). Amongst pts who received single ASCT, those with maintenance vs no maintenance demonstrated significantly better PFS (p=0.0082). Finally, pts with both t(4:14) and 17p deletion (28 pts) had a significantly decreased PFS (p= 0.0414) and a trend for decreased OS (p= 0.0621) compared to those with only one abnormality (Fig. 1C & D).Conclusions: Although adverse factors such as older age and co-morbidities likely affected the ability to perform 1 or 2 autografts and likely introduced bias into our analysis, our data nevertheless suggest that tandem ASCT is an effective approach in extending PFS and OS among HR MM pts when compared to single transplants or none at all in the real-world setting. Multivariate analysis is underway to further delineate the factors contributing to PFS and OS in HR pts. As in other transplant studies, the PFS is improved in pts who receive maintenance therapy after single ASCT. Efforts should be made to offer newly diagnosed HR MM pts a program that includes tandem transplantation, if feasible, as well as maintenance therapy post-transplant. Pts with “ultra HR” MM, i.e., those with both t(4;14) and 17p deletion, require new innovative approaches. [Display omitted] DisclosuresReece:Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Paid expert testimony, Research Funding, Speakers Bureau; Merck: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Other: Paid expert testimony, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Otsuka: Research Funding. Chen:Celgene: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Abbvie: Honoraria; Amgen: Honoraria. Kukreti:Celgene: Honoraria; Amgen: Honoraria. Prica:Janssen: Honoraria; Celgene: Honoraria. Tiedemann:BMS Canada: Honoraria; Celgene: Honoraria; Takeda Oncology: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Novartis: Honoraria. Trudel:Janssen: Research Funding; Amgen: Consultancy, Honoraria; Astellas: Research Funding; Celgene: Consultancy, Honoraria; Takeda: Honoraria; GlaxoSmithKline: Research Funding.

Sequencing of novel agents in relapsed/refractory B-cell acute lymphoblastic leukemia: Blinatumomab and inotuzumab ozogamicin may have comparable efficacy as first or second novel agent therapy in relapsed/refractory acute lymphoblastic leukemia.

The availability of novel agents (NAs), including blinatumomab and inotuzumab ozogamicin (InO), has improved the outcomes of patients with relapsed/refractory (RR) B-cell acute lymphoblastic leukemia (ALL). Because of the relative effectiveness, it is often a challenge for clinicians to determine how to best sequence these NAs with respect to efficacy and toxicity. In this multicenter, retrospective study of patients with RR ALL treated with blinatumomab, InO, or both, their efficacy as a first or second NA was compared. Among 276 patients, 221 and 55 received blinatumomab and InO, respectively, as a first NA therapy. The complete remission (CR)/complete remission with incomplete count recovery (CRi) rate was 65% and 67% for the blinatumomab and InO groups, respectively (P = .73). The rate of treatment discontinuation due to adverse events was 4% and 7% in the blinatumomab and InO groups, respectively. Ninety-two patients (43%) in the blinatumomab group and 13 patients (29%) in the InO group proceeded with allogeneic hematopoietic stem cell transplantation. The median overall survival (OS) was 15 and 11.6 months in the blinatumomab and InO groups, respectively. A subset analysis was performed for 61 patients who received both NAs (blinatumomab and then InO [n = 40] or InO and then blinatumomab [n = 21]). The CR/CRi rate was 58% for patients who received InO as the second NA and 52% for patients who received blinatumomab as the second NA. The median OS was 10.5 for patients who received InO as the second NA and 5.9 months for patients who received blinatumomab as the second NA (P = .09). Although the limited power of this study to detect a significant difference between subgroups is acknowledged, the data suggest that blinatumomab and InO may have comparable efficacy as a first or second NA therapy in RR ALL.