Comparison of Outcomes in Chronic Lymphocytic Leukemia (CLL) with the Addition of Rituximab to Initial Treatment: A Comparative Effectiveness Analysis in the Province of British Columbia (BC), Canada

Abstract Background: Clinical trials report that chemoimmunotherapy with rituximab (R) improves overall survival (OS) and progression-free survival in the treatment (tx) of symptomatic CLL patients (pts). R has been available for first-line CLL tx in BC, population 4.5 million, since 2004. We compared clinical outcomes with and without addition of R to chemotherapy in a large unselected provincial cohort of pts treated for CLL, to determine the "real world" effectiveness of addition of R to standard chemotherapy. Methods: Three large provincial databases (db) were used to identify eligible pts: the BC Provincial CLL db, the BC Lymphoid Cancer db, and the Providence Hematology CLL db. All pts who received minimum 1 cycle of first-line tx for confirmed CLL were included. Pts with > 1 hematologic malignancy (n=8) were excluded. Baseline features of pts treated with (+R) or without R (No R) were compared using Chi-squared for categorical and Kruskal-Wallis test for continuous variables. OS was calculated from date of initial tx to date of death from any cause. Treatment-free survival (TFS) was calculated from date of initial tx to date of next tx/death from any cause. Multivariate analysis (MVA) was performed using Cox proportional hazard models to evaluate the effect of R on OS/TFS, after controlling for covariates including age (³60 yrs vs <60 yrs), Rai stage (3-4 vs 0-2), CD38 status (pos vs neg), presence of 17p (17p-) and 11q (11q-) deletions, and first-line tx with purine analogs (PAs). Results: A total of 1784 pts diagnosed with CLL from 1973-2014 were identified, of which 726 pts (41%) received tx in follow-up. Of treated pts, 393 (54%) received R and 333 (46%) received chemotherapy alone. Among the No R group, tx included: chlorambucil 56%; fludarabine (F) 34%; cyclophosphamide (C)-based 8%; cladrabine 2%. Among the +R group, tx included: FR 75%; C-based + R 17%; FCR 7%; chlorambucil + R 1%. 103 pts underwent bone marrow transplant (BMT) during their tx course (19% No R vs 10% +R, P=.002). Median age at diagnosis (dx) and tx between groups were not statistically different (No R vs +R: 60.6 vs 60.8 yrs and 64.7 vs 63.9 yrs, respectively). There were no clinically significant differences in diagnostic parameters including % with elevated LDH, lymphocyte count >20x109/L , Rai stage 3-4. Median follow-up time in survivors was longer in the No R group (13.0 vs 6.8 yrs, P<.001). Among 467 pts with known CD38 status, CD38 pos was more common in +R vs No R groups (47 vs 36%, P=.02). FISH was performed in 586 pts, with no significant differences in abnormalities between tx groups. Poor-risk FISH, 17p- or 11q-, were present in 29% (No R) and 27% (+R). Median time from dx to initial tx was 2.8 yrs (range 0-20.6) in No R vs 2.5 yrs (range 0-22.7) in +R groups (P=.84). OS was longer in the +R cohort (median OS 11.8 vs 7.1 yrs, P<.001), Fig. 1. Significant improvements in OS were also seen in pts <60 yrs of age at tx (median OS 11.3 vs 3.1 yrs, P<.0001), without 17p- (median OS 9.3 vs 5.2 yrs, P<.0001), and treated with PAs (median OS 9.4 vs 6.4 yrs, P=.0001). Median TFS was longer in pts treated with R (3.3 vs 2.3 yrs, P= .004), Fig. 2, and in those without 17p- (median TFS 3.1 vs 1.3 yrs, P<.001). MVA confirmed that the addition of R to chemotherapy remained a strong independent predictor of mortality (HR 0.66, 95% CI: 0.44-0.98, P=.04) and TFS (HR 0.6, 95% CI: 0.46-0.79, P<.001) after controlling for covariates. Other independent predictors of OS included age ³60 yrs (HR 2.77, 95% CI 1.87-4.10, P<.001) and presence of 17p- (HR 1.23, 95% CI 1.62-3.76, P<.001), whereas for TFS, presence of 17p- (HR 2.08, 95% CI: 1.49-2.91, P<.001) and CD38+ (HR 1.32, 95% CI: 1.03-1.68, P=.025) were independent negative predictors. Conclusion: In this large, population based cohort of pts treated for CLL, we confirm that the addition of R to chemoimmunotherapy as initial tx significantly improves OS, resulting in a 44% lower risk of overall mortality (95% CI, 2% to 66%) after controlling for covariates. We have also demonstrated that the addition of R to first-line therapy significantly delays the time to subsequent therapy, a finding not previously reported in a population based setting to our knowledge. This study complements clinical trial [Hallek, Lancet 2010] and US Registry data [Danese, Blood 2011], demonstrating benefit of the addition of R to standard therapy for first-line treatment of CLL and shows the generalizability of such results in a real world setting. Figure 1 Figure 1. Disclosures Gerrie: Roche: Honoraria, Research Funding. Ramadan:Roche: Honoraria, Research Funding.

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Real-World Outcomes for 205 Danish Patients with Chronic Lymphocytic Leukemia Treated with Ibrutinib

Blood ◽

10.1182/blood-2019-123011 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 1767-1767

Author(s):

Kathrine Aarup ◽

Lisbeth Enggaard ◽

Robert Schou Pedersen ◽

Rasmus Heje Thomsen ◽

Olav Jonas Bergmann ◽

...

Keyword(s):

Clinical Trials ◽

Real World ◽

Cumulative Incidence ◽

Research Funding ◽

Population Based ◽

Advisory Board ◽

Lymphocytic Leukemia ◽

Travel Grant ◽

Tract Infections

Introduction Ibrutinib is an oral irreversible inhibitor of Bruton's tyrosine kinase for treatment of chronic lymphocytic leukemia (CLL). Ibrutinib has demonstrated superior efficacy for patients with TP53 aberration or relapsed/refractory (R/R) CLL; and more recently superior progression free survival (PFS) has been demonstrated compared to chemoimmunotherapy as first line therapy. However, knowledge about the outcomes and adverse events (AE) upon ibrutinib among patients at a population-based level are still limited. The aim of the here presented study is to explore outcomes of ibrutinib treatment in a population-based cohort of patients with CLL treated with ibrutinib in Denmark. Methods In this retrospective study, patients from 8 hospitals in Denmark, who were diagnosed with CLL and treated with ibrutinib from April 2014 until February 2019 were included. Medical records were retrospectively reviewed to obtain information. Patients receiving ibrutinib within clinical trials were excluded. Overall survival (OS) was defined as time from ibrutinib start to death from any cause while PFS was defined as time from ibrutinib start to progression or death from any cause. PFS and OS were analyzed with the Kaplan-Meier method while cumulative incidence was calculated with the Aalen-Johansen estimator. Results In total, 205 patients with CLL receiving ibrutinib treatment were identified from hospital records and registries. The median follow-up was 21.4 months (IQR, 11.9-32.8) and the median time on ibrutinib was 16.8 months (IQR, 6.0-28.1). The median age at treatment initiation was 72.8 years (IQR, 65.7-77.8), 128 (62.4%) were male, and 111 (63.4%) were Binet stage B/C at treatment initiation out of 175 with available information regarding clinical stage. Thirty-nine (19.0%) received ibrutinib as first-line, and 166 for R/R CLL with a median of 2 (range, 1-8) prior treatment regimens. Information on TP53 aberration was available for 149 and regarding IGHV mutation for 147 patients, 111 (74.5%) had TP53 aberration and 107 (72.8%) were IGHV unmutated. Eighty-six patients (42.0%) discontinued ibrutinib during follow-up with a median time until discontinuation of 9.3 months (IQR, 3.0-23.2). Forty-seven (54.7%) discontinued due to AEs, 19 (22.1%) due to progression (12 had progression of CLL and 7 had Richter's transformation) while the remaining 20 (23.2%) discontinued due to other reasons. The estimated cumulative incidence of discontinuation at 12 months was 24.8% (95% CI: 18.6-30.9). The estimated OS after 12 and 24 months was 88.8% (95%CI: 84.3-93.3) and 76.8% (95%CI: 70.4-83.2) and the estimated PFS after 12 and 24 months was 87.3% (95%CI: 82.5-92.1) and 72.4% (95%CI: 65.5-79.2). One hundred and eighty-eight (91.7%) experienced at least one AE, among these 45 (23.9%) experienced a grade 3+. The most common AEs were hemorrhage (tendency to bruise, epistaxis etc.) which occurred in 86 (42.0%) of all and musculoskeletal and connective tissue disorders (arthralgia, myalgia etc.) which occurred in 82 (40.0%). Thirty-one (15.1%) patients experienced atrial fibrillation while on ibrutinib and 14 (6.8%) developed hypertension. One hundred and thirty-seven patients (66.8%) had at least one infection and among these 80 (58.4%) were hospitalized with an infection. The most common infections were lower respiratory tract infections and urinary tract infections that occurred for 88 (42.9%) and 41 (20.0%). The estimated cumulative incidence for any infection was 58.9% (95%CI: 52.0-65.9) at 12 months. Conclusion This is the first study describing outcomes for a population-based cohort of CLL patients treated with ibrutinib in Denmark. Real-world studies are warranted, to confirm the results from clinical trials. In this study, patients appear to have comparable OS and types of AE compared with the RESONATE trial. Differences in frequency of AEs compared to the clinical trial may reflect the focus of clinicians in routine practice. Discontinuation in this cohort was higher compared to clinical trials but comparable to previously reported real-world studies. While ibrutinib can be safely managed in routine clinical practice, this study demonstrates that a quarter of patients discontinue treatment due to mainly AEs. Further patient training and information, and in some instances personalized treatment with other targeted agents based on adverse event profile, may improve treatment adherence. Disclosures Aarup: Research Committee, Rigshospitalet: Research Funding. Enggaard:Abbie: Other: Advisory board; Gilead: Other: Advisory board; Janssen: Other: Advisory board. Frederiksen:Gilead: Research Funding; Abbvie: Research Funding; Janssen Pharmaceuticals: Research Funding; Novartis: Research Funding; Alexion: Research Funding. Niemann:Novo Nordisk Foundation: Research Funding; AstraZeneca: Consultancy, Other: Travel Grant, Research Funding; Sunesis: Consultancy; Acerta: Consultancy; CSL Behring: Consultancy; Roche: Other: Travel Grant; Janssen: Consultancy, Other: Travel Grant, Research Funding; Gilead: Other: Travel Grant; Abbvie: Consultancy, Other: Travel Grant, Research Funding.

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Real World Treatment Patterns and Toxicity Among Elderly Patients with Multiple Myeloma

Blood ◽

10.1182/blood-2019-131114 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5571-5571

Author(s):

Jesus D Gonzalez-Lugo ◽

Ana Acuna-Villaorduna ◽

Joshua Heisler ◽

Niyati Goradia ◽

Daniel Cole ◽

...

Keyword(s):

Side Effects ◽

Real World ◽

Research Funding ◽

Treatment Patterns ◽

Line Treatment ◽

Event Free Survival ◽

First Line ◽

Treatment Change ◽

Free Survival ◽

First Line Treatment

Introduction: Multiple Myeloma (MM) is a disease of the elderly; with approximately two-thirds of cases diagnosed at ages older than 65 years. However, this population has been underrepresented in clinical trials. Hence, there are no evidence-based guidelines to select the most appropriate treatment that would balance effectiveness against risk for side effects in the real world. Currently, guidelines advise that doublet regimens should be considered for frail, elderly patients; but more detailed recommendations are lacking. This study aims to describe treatment patterns in older patients with MM and compare treatment response and side effects between doublet and triplet regimens. Methods: Patients diagnosed with MM at 70 years or older and treated at Montefiore Medical Center between 2000 and 2017 were identified using Clinical Looking Glass, an institutional software tool. Recipients of autologous stem cell transplant were excluded. We collected demographic data and calculated comorbidity burden based on the age-adjusted Charlson Comorbidity Index (CCI). Laboratory parameters included cell blood counts, renal function, serum-protein electrophoresis and free kappa/lambda ratio pre and post first-line treatment. Treatment was categorized into doublet [bortezomib/dexamethasone (VD) and lenalidomide/dexamethasone (RD)] or triplet regimens [lenalidomide/bortezomib/dexamethasone (RVD) and cyclophosphamide/bortezomib/dexamethasone (CyborD)]. Disease response was reported as VGPR, PR, SD or PD using pre-established criteria. Side effects included cytopenias, diarrhea, thrombosis and peripheral neuropathy. Clinical and laboratory data were obtained by manual chart review. Event-free survival was defined as time to treatment change, death or disease progression. Data were analyzed by treatment group using Stata 14.1 Results: A total of 97 patients were included, of whom 46 (47.4%) were males, 47 (48.5%) were Non-Hispanic Black and 23 (23.7%) were Hispanic. Median age at diagnosis was 77 years (range: 70-90). Median baseline hemoglobin was 9.4 (8.5-10.5) and 14 (16.1%) had grade 3/4 anemia. Baseline thrombocytopenia and neutropenia of any grade were less common (18.4% and 17.7%, respectively) and 11 patients (20%) had GFR ≤30. Treatment regimens included VD (51, 52.6%), CyborD (18, 18.6%), RD (15, 15.5%) and RVD (13, 13.4%). Overall, doublets were more commonly used than triplets (66, 68% vs 31, 32%). Baseline characteristics were similar among treatment regimen groups. There was no difference in treatment selection among patients with baseline anemia or baseline neutropenia; however, doublets were preferred for those with underlying thrombocytopenia compared to triplets (93.8% vs 6.2%, p<0.01). Median first-line treatment duration was 4.1 months and did not differ among treatment groups (3.9 vs. 4.3 months; p=0.88 for doublets and triplets, respectively). At least a partial response was achieved in 47 cases (63.5%) and it did not differ between doublets and triplets (61.7% vs 66.7%). In general, first line treatment was changed in 50 (51.5%) patients and the change frequency was higher for triplets than doublets (71% vs 42.4%, p<0.01). Among patients that changed treatment, 17(34.7%) switched from a doublet to a triplet; 15 (30.6%) from a triplet to a doublet and 17 (34.7%) changed the regimen remaining as doublet or triplet, respectively. There was no difference in frequency of cytopenias, diarrhea, thrombosis or peripheral neuropathy among groups. Median event-free survival was longer in patients receiving doublet vs. triplet therapy, although the difference was not statistically significant (7.3 vs 4.3 months; p=0.06). Conclusions: We show a real-world experience of an inner city, elderly MM cohort, ineligible for autologous transplantation. A doublet combination and specifically the VD regimen was the treatment of choice in the majority of cases. In this cohort, triplet regimens did not show better response rates and led to treatment change more often than doublets. Among patients requiring treatment, approximately a third switched from doublet to triplet or viceversa which suggest that current evaluation of patient frailty at diagnosis is suboptimal. Despite similar frequency of side effects among groups, there was a trend towards longer event-free survival in patients receiving doublets. Larger retrospective studies are needed to confirm these results. Disclosures Verma: Janssen: Research Funding; BMS: Research Funding; Stelexis: Equity Ownership, Honoraria; Acceleron: Honoraria; Celgene: Honoraria.

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Lenalidomide and Rituximab Maintenance Therapy after Front-Line Induction Chemoimmunotherapy in Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma

Blood ◽

10.1182/blood-2019-124489 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5470-5470

Author(s):

Julie E Chang ◽

Vaishalee P. Kenkre ◽

Christopher D. Fletcher ◽

Aric C. Hall ◽

Natalie Scott Callander ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Maintenance Therapy ◽

Research Funding ◽

Lymphocytic Leukemia ◽

Second Malignancies ◽

Front Line ◽

First Line ◽

11Q Deletion ◽

Line Chemotherapy

Introduction: Chronic lymphocytic leukemia (CLL) is incurable with standard therapy. With first-line chemotherapy, some patients (pts) may achieve durable remissions of many months/years. Lenalidomide (LEN) has improved progression-free survival (PFS) when given as maintenance (MNT) therapy after front-line chemotherapy (CALGB10404, CLLM1). The combination of LEN + rituximab (LR) has activity in relapsed CLL, hypothesizing benefit as MNT therapy after first-line chemotherapy. Methods: Adult pts ≥18 years with previously untreated CLL received induction bendamustine (B) 90 mg/m2 IV days 1 & 2 and rituximab (R) IV day 1 (375 mg/m2 cycle 1, then 500 mg/m2 cycles 2-6) for 6 treatment cycles (as few as 4 cycles allowed). MNT therapy with LR was initiated within 12 weeks after cycle 6, day 1 of BR. Criteria to start LR MNT included: neutrophils ≥1000/microliter (uL), platelets ≥75 K/uL, and creatinine clearance ≥40 mL/min. LEN was administered in 28-day cycles for 24 cycles, initially 5-10 mg daily continuous dosing, later modified to 5-10 mg on days 1-21 of each 28-day cycle in 6/2018 due to neutropenia and second malignancy risk. LEN was reduced to 5 mg every other day for toxicities at 5 mg/day. R 375 mg/m2 IV was given every odd cycle (total of 12 doses). Patients discontinuing LEN for any reason were allowed to continue R MNT per protocol. The primary endpoint is PFS with LR MNT therapy, calculated from the first day of MNT therapy until progressive disease (PD), death, or start of a new therapy. Secondary endpoints are response rate and overall survival. Results: Thirty-four pts have enrolled beginning 11/2013, with follow-up through 6/2019. Median age is 64 years, with 8 pts ≥70 years; 8 women and 26 men. CLL FISH panel is available on all pts: 14 with 13q (as sole abnormality), 9 with 11q deletion, 6 with trisomy 12, 4 with normal FISH panel and 1 with 17p deletion. Heavy chain mutation analysis is available on 11 pts: 8 unmutated, 2 mutated, 1 indeterminate. Thirty-one pts completed 4 (n=2) or 6 cycles of induction BR; 3 pts are receiving induction BR. Twenty-four pts have received MNT LR; 7 did not receive LR for reasons of PD during induction (n=2), infection (n=1), pt preference (n=2), renal insufficiency (n=1), and new carcinoma (n=1). MNT LR was completed in 7 pts; 9 pts are still receiving LR. Fourteen subjects have discontinued protocol therapy, 3 during induction due to PD (n=2) and infection (n=1), and 8 during MNT. Toxicities that led to discontinuation of LR were recurrent infections in 7 pts, including 2 events of PJP pneumonia; 4 pts had recurrent neutropenia with infections; 1 pt had neutropenia without infections. Response is assessable in 31 patients using the International Working Group Consensus Criteria. Best responses to treatment were: partial response 65% (22/34), complete response (CR)/unconfirmed CR 24% (8/34). The median number of MNT cycles received is 16. The dose intensity of LEN across total cycles received (n=278): 5 mg every other day (52.5%), 5 mg/day (43.9%), and 10 mg/day (3.6%). The most common reason for dose reduction or dose holding was neutropenia. Most common Gr 3/4 toxicities (reported as events Gr3/Gr4) during MNT therapy were: neutropenia (20/20), leukopenia (19/4), febrile neutropenia (3/1), and infections (11/-). The majority of Gr3 infections were pneumonia/respiratory (n=5). One event of disseminated herpes zoster occurred. Second malignancies during MNT included: basal cell CA (n=1), squamous cell carcinoma (n=5), and colon cancer (n=1). No unexpected second malignancies were observed in pts receiving LR. Two-year PFS (defined from day 1 of MNT therapy) is 90% (95% confidence interval [CI] 0.78-1), and the median follow-up for 24 patient who started maintenance therapy is 1.79 years (95% CI 1.53-2.7). There have been no deaths. Conclusion: The combination of LR is effective in sustaining remissions after a BR induction in previously untreated CLL, but with frequent neutropenia and infections even at low doses of LEN. Most patients discontinuing MNT did so due to neutropenia and/or infections. A shorter planned interval of MNT LR (i.e., 6-12 months) may confer similar benefit to extended dosing that is more tolerable. Pts at high risk for short remissions after front-line chemotherapy (e.g., unmutated heavy chain status, 11q deletion and/or failure to achieve minimal residual disease after induction) may be the populations for which LR MNT therapy is most appropriate. Disclosures Chang: Genentech: Research Funding; Adaptive Biotechnologies: Research Funding; Celgene: Research Funding. OffLabel Disclosure: Lenalidomide administered as maintenance therapy for first treatment of CLL/SLL.

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Observational Prospective Registry for the Assessment of the Clinical Impact of Starting Anti-Myeloma Treatment at Biological Relapse

Blood ◽

10.1182/blood.v124.21.4765.4765 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4765-4765

Author(s):

Adrian Alegre ◽

Merche Gironella ◽

Juan Miguel Bergua ◽

Esther Gonzalez ◽

Fernando Escalante ◽

...

Keyword(s):

Bone Marrow ◽

Board Of Directors ◽

Median Time ◽

Research Funding ◽

Marrow Transplant ◽

Clinical Relapse ◽

First Line ◽

Advisory Committees ◽

Free Survival

Abstract Introduction: Despite the great medical advances associated with the introduction of thalidomide, bortezomib (BORT), and lenalidomide (LEN) for the treatment of multiple myeloma (MM), it remains an incurable disease. Most patients (pts) show disease progression, consistent with the clinical evolution of MM, and only a low percentage achieve long-term responses and extended progression-free survival (PFS). The heterogeneous nature of MM in both the clinical and biological setting is reflected in the heterogeneity of MM relapses. The International Myeloma Workshop Consensus Panel (Rajkumar, Blood 2011) states that treatment (Tx) shall begin either at clinical relapse with symptoms (clinR), or in the event of asymptomatic relapse with significant paraprotein relapse, biological relapse (BR). The purpose of this Spanish registry is to describe MM relapse patterns comparing the impact of Tx decisions in pts who meet the criteria for biological relapse (BR) according to IMWG criteria with those in whom Tx was delayed until clinical relapse (clinR). Here, the preliminary results of this study are presented. Methods: MM pts in (or previous to) first or second BR who have achieved ≥ PR since their last Tx are eligible for inclusion in this observational prospective registry at the time BR is detected. Evaluations performed at least bi-monthly are mandatory. A total of 41 Spanish sites participated in the registry following approval from their independent ethics committees, with 410 pts expected to be included, without physician’s decision of prescribing Tx affecting the inclusion. The main objective of the registry is to assess the time to progression (TTP) from the start of anti-MM Tx at the onset of asymptomatic BR vs. the start of Tx at the time of clinR. Secondary objectives are to describe demographics of BR; to assess the median time elapsing from BR to clinR; to assess overall response rate (ORR), event-free survival (EFS), PFS, overall survival (OS) at BR and at clinR (if appropriate); to asses safety and quality of life (QoL) using 2 validated questionnaires (European Organisation for Research and Treatment of Cancer [EORTC] QLQ-C30 and QLQ-MY24); to document the tolerability profile of the Tx; and to describe the use of associated resources. Here, we summarize baseline characteristics and preliminary results from 83 pts (out of 126 registered pts) who had basal data in the registry at the time of this report. Results: Overall, 79% of pts presented with a BR and 21% were in a bi-monthly watchful waiting follow up. The mean age of pts was 67 years, 53% were female, 57% were in first relapse, 43% and 27% had an ECOG performance status (PS) of 0 and 1, respectively, while the ECOG PS was unknown in 30% of pts at the time of this report. In total, 30% of pts had ISS stage I, 26% had ISS stage II, and 22% had ISS stage III, while ISS stage data were not available or unknown for 12% and 10% of pts, respectively. MM types were IgG Κ (37% of pts), IgG λ (23%), IgA Κ (13%), IgA λ (9%), and type was unknown in 17% of pts. 28% of IgG/IgA MM types were Bence-Jones. Cytogenetic risk assessments were available in 66% of pts. Among those pts with a BR, 51% received active Tx without waiting for a ClinR. First-line Tx was BORT-based in 70% of pts. Overall, 55% of pts had undergone autologous stem cell transplantation, 15% had received consolidation Tx and 34% had received maintenance Tx. After first-line Tx, 17% of pts achieved a stringent complete response (sCR), 31% achieved a CR, 24% achieved a very good partial response (VGPR), and 10% achieved a PR. The median time to BR was 24.53 months. Most (63%) pts who registered after second relapse received LEN-based Tx. Conclusions: To our knowledge, this is the first prospective study in MM to evaluate BR as well as the effects of Tx based on the decision to start Tx at BR vs. clinR. In this preliminary cohort, the physicians’ decision to start active Tx at BR, before the onset of clinR in 50% of cases, was noteworthy. Further follow-up is needed to identify the differences between these two strategies. Updated clinical results will be presented at the meeting. MM-BR Study, Spanish Myeloma Group-GEM/PETHEMA Bibliography Alegre A, et al. Haematologica. 2002;87:609-14. Brioli A, et al. Blood. 2014;123:3414-9. Fernández de Larrea C, et al. Bone Marrow Transplant. 2014;49:223-7. Lenhoff S, et al. Haematologica. 2006;91:1228-33. Rajkumar SV, et al. Blood. 2011;117:4691-5. Zamarin D, et al. Bone Marrow Transplant. 2013;48:419-24. Disclosures Alegre: Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Jansen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Lahuerta:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Ruiz:Celgene: Celgene Stock options as part of the employee's compensation plan Other, Employment. Vilanova:Celgene: Contracted by Celgene Other.

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A Phase Ib/II Study of Combined Obinutuzumab (Gazyva) and High-Dose Methylprednisolone (HDMP) As Treatment for Patients with Chronic Lymphocytic Leukemia (CLL)

Blood ◽

10.1182/blood.v128.22.2051.2051 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2051-2051 ◽

Cited By ~ 1

Author(s):

Januario E. Castro ◽

Michael Y. Choi ◽

Carlos I. Amaya-Chanaga ◽

Natalie Nguyen ◽

Colin MacCarthy ◽

...

Keyword(s):

Chronic Lymphocytic Leukemia ◽

Research Funding ◽

Lymphocytic Leukemia ◽

Phase Iii ◽

High Dose ◽

Free Survival ◽

Phase Ib ◽

High Dose Methylprednisolone ◽

Grade 3

Abstract High-dose methylprednisolone (HDMP) and rituximab (R) is an effective non-myelosuppressive treatment regimen for patients (pts) with chronic lymphocytic leukemia (CLL). Also, this combination has shown activity even in pts who have adverse leukemia-cytogenetics, such as del17p. Phase III studies have demonstrated that CLL pts treated with chlorambucil and obinutuzumab-Gazyva (G), another anti-CD20 mAb, had a superior outcome than comparable pts treated with R-chlorambucil. We hypothesized that G-HDMP is well-tolerated and effective in the treatment of pts with CLL. Accordingly, we initiated an open-label phase Ib/II clinical study. A total of 40 pts were enrolled in two cohorts of 20 pts each (previously untreated (PU) and relapsed/refractory (RR) CLL) and treated with HDMP 1 g/m2on Day 1-3 of cycles 1-4 (28 days/cycle) and G administered based on FDA dosing recommendations for 6 cycles. The pts had a median age of 67 years + 9.1 in the RR cohort and 63 years + 8.3 in the PU cohort. The median baseline absolute lymphocyte count was 30.7 + 7.3 x1,000/mm3 for pts in the RR cohort and 47.6 + 19.7 x1,000/mm3for pts in the PU cohort. Pts showed the following cytogenetic abnormalities: del(17p) in 30% RR vs. 0% PU, del(13q) in 60% RR vs. 70% PU, del(11q) in 20% RR vs. 35% PU, and trisomy 12 in 15% RR vs. 20% PU. Most AEs were grade 1-2 (RR=87%; PU=93%) without development of dose-limiting toxicities. Only two pts needed therapy discontinuation. One pt due to pulmonary embolism and the second pt due to asymptomatic gastrointestinal bleeding that required blood transfusion and resolved spontaneously. Grade 1-2 G-infusion-related reactions (IRR) were observed in 40% and 80% of pts in the RR and PU cohorts, respectively. Grade 3-4 IRR were observed in 10% of pts in the PU cohort only. We observed cytopenias (neutropenia grade 3-4: RR=55%, PU=40%; thrombocytopenia grade 3-4: RR=35%, PU=20%; and anemia grade 3-4: RR=0%, PU=0%). There were no cases of febrile neutropenia. Two pts (10%) in the RR cohort and one pt (5%) in the PU cohort developed infection grade 1-2 that was treated with oral antibiotics but did not require study treatment discontinuation. The most frequent non-hematological adverse events (AEs) were transaminitis, hyperglycemia, and electrolyte alterations (grade 1-2). There were no treatment related deaths in either cohort. The response assessment was performed in all 40 pts by iwCLL criteria. The ORR was 100% in the PU cohort and 95% in the RR cohort. 70% of the pts in the PU cohort and 85% of the pts in the RR cohort achieved a PR. CR was observed in 30% and 10% of the pts in the PU and RR cohorts, respectively. One pt (5%) in the RR cohort and four pts (20%) in the PU cohort achieved MRDneg status (<0.01% CLL in the bone marrow by multiparameter flow cytometry). Only one pt in the RR cohort achieved SD. At a median follow-up of 12.2 months, the RR cohort had a median Progression Free Survival (PFS) of 13.6 months and median Treatment Free Survival (TFS) of 14.7 months; the median Overall Survival (OS) has not been reached. In the PU cohort, the median PFS, TFS and OS have not been reached. One pt from the RR cohort and one pt from the PU cohort died during the follow-up period due to disease progression. G-HDMP was well tolerated and all 40 pts showed hematological and clinical responses during the study treatment without development of unexpected AEs. In both cohorts, most of IRR were grade 1-2 and severe IRR (grade 3-4) were much less compared with previously published data (G-chlorambucil / CLL-11 study). Compared to pts in the CLL-11 study, cytopenias appeared to be more frequent, however, the rate of infection and need for IV antibiotics or hospitalizations was lower. Of note, the eligibility criteria allowed pts with severe cytopenias and transfusion requirement to participate in our study. Response in PU pts were higher in terms of ORR, CR and CR-MRDnegativecompared with the data from the CLL-11 study and suggests a possible synergistic activity between G and HDMP. Overall, G-HDMP was well tolerated in the PU and RR CLL pts with a lower rate of IRR making this regimen more manageable in the outpatient setting. Responses were higher than previously reported in PU pts. Responses in RR pts appear to be comparable to our previous studies using R-HDMP. Our data supports G-HDMP as an alternative combination regimen for the treatment of CLL pts. Disclosures Kipps: Celgene: Consultancy, Honoraria, Research Funding; Pharmacyclics, LLC, an AbbVie Company: Consultancy, Honoraria; Gilead: Consultancy, Honoraria, Speakers Bureau; AbbVie: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria.

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DOP54 Real-world effectiveness of thiopurine monotherapy in Crohn’s Disease: Is there still a place for thiopurines in the biological era?

Journal of Crohn s and Colitis ◽

10.1093/ecco-jcc/jjab073.093 ◽

2021 ◽

Vol 15 (Supplement_1) ◽

pp. S089-S090

Author(s):

A Rezazadeh Ardabili ◽

S F G Jeuring ◽

Z Mujagic ◽

M J L Romberg-Camps ◽

A A van Bodegraven ◽

...

Keyword(s):

Crohn’S Disease ◽

Maintenance Therapy ◽

Treatment Option ◽

Real World ◽

Population Based ◽

Line Treatment ◽

First Line ◽

First Line Treatment

Abstract Background In current guidelines, thiopurines are still recommended as first-line maintenance therapy for patients with Crohn’s disease (CD). Due to their lack of immunogenicity, oral administration route and low costs, thiopurines are an attractive first-line treatment option. However, in recent studies the position of thiopurine monotherapy in CD has been questioned as a result of relatively lower overall effectiveness rates compared to ulcerative colitis. Real-world long-term effectiveness data substantiating the use and position of thiopurines in CD management remain sparse. We assessed long-term effectiveness of thiopurine monotherapy in CD using the population-based IBD South-Limburg (IBDSL) cohort. Methods All CD patients in the IBDSL cohort starting thiopurine monotherapy as first-line maintenance therapy between 1991–2014 were included. Thiopurine monotherapy was defined effective if either: (1) no escalation to biological treatment, (2) no course of corticosteroids, (3) no resective surgery or, (4) no hospitalization for active disease was required whilst on thiopurine treatment. Patients with early treatment discontinuation (i.e. <3 months) were identified, including reason of discontinuation. Long-term effectiveness was assessed adjusting for differences in follow-up between patients using Kaplan-Meier analysis. Potential risk factors for therapy failure were identified using Cox regression. Results In total, 643/1162 (55.3%) CD patients (median follow-up: 8.5 years IQR 5.0–13.2) received first-line thiopurine monotherapy after a median of 9.7 months (IQR 3.2–31.3) after diagnosis. Therapy was discontinued within three months in 164 patients (25.5%), mainly due to adverse events [Figure 1]. Thiopurine monotherapy was effective for the duration of treatment in 229/479 (35.6%) patients, corresponding to estimated effectiveness rates of 62.9%, 43.9% and 31.2% after 1, 5 and 10 years, respectively [Figure 1–2]. No significant difference in effectiveness was observed after stratifying for era of thiopurine initiation (pre-biological (1991–1998) vs. biological (>1999) era, p=0.84). Factors associated with thiopurine failure were stricturing disease (aHR 1.41, 95%CI 1.01–1.96) and upper GI involvement (aHR 1.52, 95%CI 1.02–2.28) at diagnosis. During follow-up, 40/229 patients with a durable response discontinued treatment due to quiescent disease. Of these, 35 patients (87.5%) remained without treatment 24 months after discontinuation. Conclusion Real-world data from this population-based study demonstrate that thiopurine monotherapy remains an effective and durable first-line treatment option for CD, even in the biological era. These results should be considered in the ongoing discussion regarding the position of thiopurine therapy.

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Chemoimmunotherapy for Patients with Chronic Lymphocytic Leukemia: MD Anderson Experience Beyond FCR300

Blood ◽

10.1182/blood.v128.22.2047.2047 ◽

2016 ◽

Vol 128 (22) ◽

pp. 2047-2047 ◽

Cited By ~ 1

Author(s):

Dai Chihara ◽

Philip A Thompson ◽

Hagop M. Kantarjian ◽

Susan M. O'Brien ◽

Alessandra Ferrajoli ◽

...

Keyword(s):

Cumulative Incidence ◽

Research Funding ◽

Risk Model ◽

Lymphocytic Leukemia ◽

Cox Proportional Hazards Model ◽

High Dose ◽

First Line ◽

Ighv Gene ◽

The Impact

Abstract Background: Novel, targeted therapies, such as ibrutinib, have transformed outcomes for patients with relapsed CLL and for older and unfit patients in the first-line setting. However, chemoimmunotherapy (CIT) remains the standard-of-care in fit patients. We reported that a subgroup of patients with IGHV mutated CLL experience prolonged PFS and potential cure after first-line CIT withfludarabine, cyclophosphamide and rituximab (FCR). However, FISH data was not available for this cohort of patients. Accurate knowledge of which patients are likely to experience prolonged PFS after FCR is essential to better select patients who may benefit from CIT in the era of novel therapies. Patients and Methods: We analyzed 492 patients who were treated on six clinical trials of first-line CIT between 2004 and 2015. Treatments were FCR, (n=277) FCR with high dose rituximab (n=65), FCR plusmitoxantrone (n=30), FCR plusalemtuzumab (n=60) and FCR with GM-CSF (n=60). Progression-free survival (PFS) and overall survival (OS) were calculated and pretreatment characteristics were evaluated for association with survival outcomes using a Cox Proportional Hazards model. Cumulative incidence was calculated by competing risk (death without event) regression analysis. Results: The median age of patients was 59 (range 28-84). Sixty-seven percent of the patients were male, 33% of the patients had mutated IGHV gene. Thirty percent of patients had del(13q), 19% had Trisomy12, 21% had del(11q), 8% had del(17p) and 21% were negative by FISH. Fifty-nine percent of patients received six cycles of CIT. With a median follow up duration of 6.2 years, the median PFS and OS were 6.3 years and not reached, respectively. Recently reported risk model by Rossi and colleagues using IGHV mutation status and FISH results (Blood 2015) discriminated PFS very well; 5-year PFS for low risk {mutated without del(11q)}, intermediate risk {unmutated or del(11q)} and high risk group {del(17p)} were 81%, 45% and 22%, respectively. Of note, there was a plateau in PFS after 8 years in patients with mutated IGHV gene, with 10-year PFS of 63% (Figure A). There was a significantly improved OS after relapse by the time. Three-year OS in patients who started salvage chemotherapy in 2004 to 2012 and 2012 to 2016 were 59% and 83%, respectively, suggesting the impact of improved salvage treatment options, particularly B cell signaling pathway inhibitors (Figure B). Five-year cumulative incidence of Richter transformation (RT) and AML/MDS was 4.8% and 4.2%, respectively (Figure C, D). There was a difference in onset for these two complications; 52% of RT occurred within 2 years, while 62% of AML/MDS occurred in 2-4 years after CIT. Overall, 110 patients (22.4%) died during the follow-up; the three major causes of death were CLL progression (4.9%), Richter transformation (3.7%) and AML/MDS (3.3%). Conclusion: Patients with mutated IGHV gene and who do not have del(11q) or del(17p) have favorable outcomes and demonstrate a plateau on the PFS curve, consistent with prior studies. Effective salvage therapy has improved outcomes at relapse, but the development of RT and AML/MDS remain major causes of mortality in CLL patients. Given favorable outcomes for patients with mutated IGHV gene treated with FCR, further studies are warranted to identify predictors of non-response among the mutated patients, risk factors for development of AML/MDS and RT and whether choice of first-line therapy can modulate this risk. Disclosures Thompson: Pharmacyclics: Consultancy, Honoraria. O'Brien:Janssen: Consultancy, Honoraria; Pharmacyclics, LLC, an AbbVie Company: Consultancy, Honoraria, Research Funding. Jain:Servier: Consultancy, Honoraria; Novimmune: Consultancy, Honoraria; Incyte: Research Funding; Celgene: Research Funding; ADC Therapeutics: Consultancy, Honoraria, Research Funding; Genentech: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Seattle Genetics: Research Funding; Novartis: Consultancy, Honoraria; Abbvie: Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; BMS: Research Funding; Infinity: Research Funding. Wierda:Abbvie: Research Funding; Novartis: Research Funding; Acerta: Research Funding; Gilead: Research Funding; Genentech: Research Funding.

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Real-World Treatment Patterns from the HUMANS Study in Multiple Myeloma in Denmark

Blood ◽

10.1182/blood-2019-121953 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5030-5030

Author(s):

Niels Abildgaard ◽

Anders Waage ◽

Markus Hansson ◽

Pekka Anttila ◽

Mate Szilcz ◽

...

Keyword(s):

Multiple Myeloma ◽

Real World ◽

Treatment Duration ◽

Research Funding ◽

Population Based ◽

Treatment Patterns ◽

Line Treatment ◽

First Line ◽

Real World Evidence ◽

First Line Treatment

Introduction Current treatment for multiple myeloma (MM), an incurable but treatment sensitive plasma cell cancer, aims to extend time to disease progression, prolong survival and improve quality of life. Nevertheless, epidemiological knowledge regarding MM treatment is mostly derived from randomized controlled trials, which are limited by strict inclusion criteria, study designs that assess drug efficacy in optimal clinical settings, and short follow-up. Current treatment options for MM are associated with complex and varying treatment-related side effect profiles. However, real-world evidence is available only for a limited selection of treatment regimens. Thus, there is a need for studies to further investigate treatment patterns in clinical settings that reflect real-world practice. The Health Outcome and Understanding of Myeloma - a multi-national real-world evidence (HUMANS) study - aimed to characterize patient characteristics, treatment patterns, and outcomes for newly diagnosed patients with MM who received first-line treatment. Here we report first results from the Danish study. Methods This population-based, retrospective, longitudinal, observational study used secondary data from the Danish Cancer Register (DCR) and National Patient Register (NPR) for patients diagnosed with MM. Patients were stratified by autologous stem cell transplantation (ASCT) and pharmacological treatment (bortezomib-based, lenalidomide-based, or other first-line therapy) and characterized using descriptive statistics. To analyse recent treatment patterns and also include patients with long duration before treatment start, eligible patients had first MM diagnosis from 2005-2016 in the NPR and DCR (diagnosis date identified from the DCR), first MM-specific treatment from 2010-2018 in the NPR, no other hematologic cancer records in the NPR and DCR, and no MM treatment before diagnosis. Treatment duration (time between start and end of treatment period, with set grace period of 60 days and assumed treatment supply of 7 and 28 days per treatment event for bortezomib and lenalidomide, respectively) and overall survival (OS) were estimated by Kaplan-Meier method. Results The study population comprised 2,451 patients with MM, of which 887 patients (36%) underwent ASCT. In the non-ASCT population (n=1564), the majority (n=838, 54%) received bortezomib as first-line treatment, 102 patients (7%) received lenalidomide, and for 631 patients (40%), first-line treatment could not be identified (referred to as the other non-ASCT cohort). Mean (standard deviation) age overall at first MM diagnosis was 68 (±11) years, and was 72 (±8), 75 (±9), 77 (±7), and 59 (±8) years in the bortezomib, lenalidomide, other non-ASCT and ASCT cohorts, respectively. A higher number of men (57%) than women were diagnosed with MM. From 2015 onwards, the proportion of patients who received lenalidomide increased, whereas for patients who received other MM specific drugs, the proportion decreased (see Table 1). The median OS (95% confidence interval [CI]) from administration of first-line treatment for the bortezomib and lenalidomide cohorts was 52.9 (46.2-58.2) and 69.3 (54.7-108.4) months, respectively. For the ASCT cohort the median OS was 117.2 (104.2-133.8) months from MM diagnosis. Patients followed a once or twice weekly regimen of bortezomib treatment, i.e. 3/4 or 7 days between treatments (Figure 1). Patients in the bortezomib cohort remained treated with a median bortezomib treatment duration of 4 months (CI 4.04-4.60) and an estimated 10% remained on treatment at 10 months. In the lenalidomide cohort, patients remained treated with a median duration of 7 months (CI 4.67-10.12) and an estimated 10% remained on treatment at 23 months (Figure 2). Conclusion In this study, we present population-based treatment patterns and outcomes for MM in Danish clinical practice. The 4 month median treatment duration of bortezomib was lower than the target treatment suggested by prior clinical trials. The differences in overall survival and treatment duration should be interpreted with caution, as patients in the different cohorts have varying baseline characteristics. Linked data from the DCR and NPR may provide real-world evidence of treatment patterns in clinical practice. Research regarding time to progression in a multiple myeloma real-world setting is warranted. Disclosures Abildgaard: Amgen: Research Funding; Takeda: Research Funding; Janssen: Research Funding; Celgene: Research Funding. Szilcz:Parexel International: Employment. Ma:Parexel International: Employment. Ørstavik:Takeda Pharmaceuticals International AG: Employment. Bent-Ennakhil:Takeda Pharmaceuticals International AG: Employment. Freilich:Parexel International: Employment. Gavini:Takeda Pharmaceuticals International AG: Employment.

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Real-World Efficacy of Venetoclax-Based Regimens in Patients with Chronic Lymphocytic Leukemia in Israel: A Multicenter Prospective Study

Blood ◽

10.1182/blood-2021-146504 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3727-3727

Author(s):

Yair Herishanu ◽

Neta Goldschmidt ◽

Gilad Itchaki ◽

Itai Levi ◽

Ariel Aviv ◽

...

Keyword(s):

Real World ◽

Interim Analysis ◽

Research Funding ◽

Lymphocytic Leukemia ◽

Phase Iii ◽

Publicly Traded ◽

Phase Iii Clinical Trials ◽

Medical Centers ◽

Grade 3

Abstract Background: The BCL-2 inhibitor venetoclax in combination with an anti-CD20 monoclonal antibody (rituximab or obinutuzumab) has demonstrated superior outcomes and manageable safety as compared to chemo-immunotherapy in phase III clinical trials for chronic lymphocytic leukemia (CLL). Moreover, venetoclax-based regimens induced high rates of undetectable minimal residual disease (uMRD). Prospective data on the effectiveness of venetoclax-based regimens specifically with regard to achieving uMRD in a real-world setting are still lacking. Here we report the first interim analysis for efficacy and safety of an ongoing nationwide real-world study of venetoclax based therapy for CLL/small lymphocytic lymphoma (SLL). Method: A prospective observational nationwide multicenter study. Treatment-naïve (TN) and relapsed/refractory (R/R) CLL/SLL patients were enrolled in 13 medical centers in Israel. The primary endpoint was clinical response, per physician assessment 12-months after the initiation of venetoclax treatment. Key secondary endpoints included progression free survival (PFS), overall survival (OS) and uMRD as assessed at a central laboratory by 8-color flow-cytometry. Results: Between February 10, 2019, and Jun 17, 2021 (data cut), 199 CLL/SLL patients were enrolled from 13 medical centers in Israel to receive venetoclax based therapy. The study included 83 TN and 116 R/R evaluable CLL/SLL patients with a median age of 69 years (range, 34-85) and 70.5 years (range, 25-91), respectively (Table 1). R/R patients had received a median of one prior therapy with a range up to 8, of these patients 60 (51.7%) were previously treated with a B-cell receptor inhibitor (BCRi) including ibrutinib in 52 (44.8%) and idelalisib in combination with rituximab in 6 (5.2%). TN patients had been treated with venetoclax in combination with obinutuzumab (92.8%) or rituximab (4.8%) and R/R patients received either venetoclax with rituximab (60.3%) or obinutuzumab (9.5%), venetoclax monotherapy (25.8%) or triple therapy with venetoclax, rituximab and ibrutinib in 5 (4.3%). Dose escalation of venetoclax to the recommended dose of 400 mg daily was achieved in 80.7% (n=67) of TN and 81% (n=94) of R/R patients. The median duration of ramp-up was 38 and 42 days in TN and R\R patients, respectively. Prior to therapy, tumor lysis syndrome (TLS) risk was considered high in 12% and 29.3% of TN and R/R patients, respectively (Table 1). Laboratory TLS occurred in one TN patient and 4 R/R patients, whereas 3 of the R/R patients experienced clinical TLS. Nineteen TN and 75 R/R patients had a follow-up of at least 12 months or discontinued study prematurely. The 12-month overall response rate (ORR) for TN and R/R patients was 89.5% [complete response (CR) 13 (68.4%), partial response (PR) 4 (21.1%)] and 73.3% [CR 37 (49.3%), PR 18 (24%)], respectively. In the R/R cohort, the 12-month ORR among assessed patients was 67.6% (25/37) in BCRi-exposed versus 85.7% (30/35) in BCRi-naïve patients. At 12 months, peripheral blood uMRD (<0.01%) was achieved in 12 out of 14 (85.7%) TN and 26 out of 38 (68.4%) R/R evaluated patients. At a median follow-up of 5.1 months (range, 0.5-15.6) for TN and 10.1 months (range, 0-25.7) for R/R patients, the median PFS and OS, for both cohorts have not been reached. The estimated 12-month PFS was 90.9% for TN and 81.1% for R/R patients. For R/R patients with prior exposure to BCRi, the estimated 12-month PFS was 69.6% versus 94.8% in BCRi-naïve patients (figure 1). Grade ≥3 adverse events (AEs) were reported in 34.9% of TN patients and 43.9% R/R patients. The most frequent grade ≥3 AEs documented were neutropenia (TN: 19.2% and R/R 17.2%), infections (TN: 4.8% and R/R: 21.5%) and febrile neutropenia (TN: 2.4% and in R/R: 2.6%). COVID-19 occurred in 7 patients including one death. At the time of data cut, 10 deaths occurred, one TN and 9 R/R patients. Causes for death included infections (5 patients), disease progression (2 patients), acute myeloid leukemia/ myelodysplastic syndrome (2 patients) and a soft-tissue sarcoma (1 patient). Conclusions: This first interim analysis of our ongoing prospective real-world study of venetoclax-based treatment for TN and R/R CLL/SLL, demonstrates high efficacy together with a high proportion of undetectable MRD levels and a favorable toxicity profile. These efficacy results are comparable to those reported in previous Phase III clinical trials for CLL, with no new safety signals. Figure 1 Figure 1. Disclosures Herishanu: AbbVie: Consultancy, Honoraria, Research Funding; Janssen: Honoraria; Roche: Honoraria; AstraZeneca: Honoraria. Goldschmidt: AbbVie: Consultancy, Research Funding. Itchaki: Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. Levi: AbbVie: Consultancy, Research Funding. Aviv: AbbVie: Honoraria, Research Funding. Fineman: AbbVie: Research Funding. Dally: AbbVie: Honoraria, Research Funding. Tadmor: Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding. Ruchlemer: AbbVie: Consultancy, Honoraria, Research Funding. Abadi: AbbVie: Honoraria, Research Funding. Shvidel: AbbVie: Honoraria, Research Funding. Braester: AbbVie: Honoraria, Research Funding. Cohen: AbbVie: Current Employment, Current equity holder in publicly-traded company. Frankel: AbbVie: Current Employment, Current equity holder in publicly-traded company. Ofek: AbbVie: Current Employment, Current equity holder in publicly-traded company. Berelovich: AbbVie: Current Employment, Current equity holder in publicly-traded company. Grunspan: AbbVie: Current Employment, Other: May hold equity. Benjamini: Janssen: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding.

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Outcomes of FOLFIRINOX (FFX) and gemcitabine+nab-paclitaxel (GnP) in initially unresectable locally advanced pancreatic cancer (uLAPC): A population-based study.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.4_suppl.394 ◽

2017 ◽

Vol 35 (4_suppl) ◽

pp. 394-394

Author(s):

Kelvin K. Chan ◽

Helen Guo ◽

Jaclyn Marie Beca ◽

Ruby Redmond-Misner ◽

Wanrudee Isaranuwatchai ◽

...

Keyword(s):

Pancreatic Cancer ◽

Surgical Resection ◽

Real World ◽

Conversion Rate ◽

Population Based ◽

Income Quintile ◽

World Population ◽

First Line ◽

Funding Program

394 Background: Data regarding the benefits of FFX and GnP in patients (pts) with initially uLAPC is limited. FFX and GnP have been universally publicly funded for first-line uLAPC in Ontario, Canada, since April 2015. The aims of this study are to determine (1) the overall survival (OS) of pts receiving FFX and GnP, (2) the surgical conversion rate of FFX and GnP, and (3) whether resection is associated with better OS in pts with uLAPC in an unselected, real world population. Methods: All pts in Ontario who started first-line FFX, GnP or gemcitabine (G) for uLAPC between April 2015 and March 2016 were identified in Cancer Care Ontario’s New Drug Funding Program database. They were linked to the Ontario Cancer Registry and other population-based databases to ascertain baseline characteristics (age, sex, performance status (PS), locating of tumor, income quintile, and rural residence) and outcomes (pancreatic cancer resection and vital status). Crude and adjusted models of OS were generated using Kaplan-Meier the method and Cox regression. Surgical resection was modelled as a time-dependent variable to examine its association with OS. Results: We identified 147 pts with uLAPC (mean age = 65, 44% female, 31% ECOG PS 0, 61% PS 1, 60% pancreatic head). Ninety (61.2%), 40 (27.2%) and 17 (11.6%) patients were treated with FFX, GnP and G, respectively. With a median follow-up of 7.5 months, median OS was not reached. The 6-month OS rate was 87.8%, 75.1% and 76.4% for FFX, GnP and G, respectively (p = 0.33). Resection occurred in 12 (8.2%) patients, with 10 (11.1%) and 2 (5.0%) treated with FFX and GnP, respectively ( p= 0.34). Surgical resection after initial chemotherapy was not associated with better OS in multivariable analysis (HR 0.26, 95%CI 0.03-1.98, p= 0.19). Conclusions: Pts with uLAPC treated with FFX and GnP appeared to have a reasonable OS in the real world, with > 75% of pts alive at 6 months. Surgical conversion rate in this unselected population appeared to be less than other single institutional studies. The current findings do not appear to show an early surgical benefit, but longer follow-up will be required to assess the potential long-term benefit of surgery.

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