Median Time To Next Therapy Research Articles

PB2137 SUBGROUP ANALYSIS OF PATIENTS FROM CANADA AND THE UNITED STATES IN THE PHASE 3 FIRST TRIAL IN TRANSPLANT‐INELIGIBLE NEWLY DIAGNOSED MULTIPLE MYELOMA

Background:The pivotal FIRST trial, the largest study conducted in transplant‐ineligible (TNE) patients (pts) with newly diagnosed multiple myeloma (NDMM), examined lenalidomide plus low‐dose dexamethasone until disease progression (Rd continuous), Rd for 18 cycles (Rd18), and melphalan, prednisone, and thalidomide (MPT). The study, conducted in 18 countries in Europe, North America, and Asia Pacific, demonstrated that Rd continuous significantly improved progression‐free survival (PFS) vs MPT (median 26.0 vs 21.9 mos; HR, 0.69; 95% CI, 0.59‐0.79; P < .00001). PFS was similarly extended for Rd continuous vs Rd18 (median 21.0 mos; HR, 0.70; 95% CI, 0.60‐0.81). Furthermore, median overall survival (OS) was significantly longer with Rd continuous vs MPT (median 59.1 vs 49.1 mos; HR, 0.78; 95% CI, 0.67‐0.92; P = .0023). These results support the use of frontline oral, alkylator‐free continuous therapy for TNE NDMM pts and established Rd continuous as a standard of care as reflected by clinical guidelines in Canada, the US, and Europe.Aims:To report outcomes in the subset of patients from Canada and the US.MethodsPts with TNE NDMM were randomized 1:1:1 to Rd continuous (with lenalidomide given on days 1‐21 of 28‐day cycles until disease progression), Rd18 (with lenalidomide given on days 1‐21 of eighteen 28‐day cycles), or MPT (twelve 42‐day cycles). Rd18 and MPT were both 72 weeks in duration. Stratification factors included country and Rd continuous vs MPT was the primary comparison. The primary endpoint was PFS and secondary endpoints included OS, time to next therapy (TTNT) and safety. Time from randomization to second progression or death (PFS2) was an exploratory analysis. Response assessment used for PFS and PFS2 analysis was determined by investigators based on International Myeloma Working Group criteria. Data is presented as of the January 21, 2016 cutoff used for the final OS analysis.Results:A total of 312 pts from Canada (n = 252) and the US (n = 60) were enrolled (104 in each arm). Consistent with results from the intent‐to‐treat (ITT) analysis, the Canada/US subgroup also demonstrated a significant improvement in PFS with Rd continuous vs MPT (median 29.3 vs 20.2 mos; HR, 0.69; 95% CI, 0.49‐0.97; P = .03326) and an improvement vs Rd18 (median 21.9 mos; HR, 0.72; 95% CI, 0.51‐1.02; Table). Median OS was 56.9 vs 46.8 mos for Rd continuous vs MPT (HR, 0.77; 95% CI, 0.53‐1.11; P = .15346). Median PFS2 was longer for Rd continuous vs MPT (median 39.3 vs 35.1 mos; HR, 0.69; 95% CI 0.50‐0.95) as was TTNT (median 39.1 vs 24.6 mos; HR, 0.54; 95% CI, 0.37‐0.78). Additional details, including safety data, will be presented at the meeting.Summary/Conclusion:In the Canada/US subpopulation of pts from FIRST, Rd continuous extended median PFS by 9 mos vs MPT and > 7 mos vs Rd18. Rd continuous also delayed median TTNT > 14 mos and resulted in a longer PFS2 vs MPT, suggesting that the benefit from frontline Rd continuous is maintained at relapse. These results are consistent with that from the ITT population confirming the advantage of Rd continuous vs MPT in the Canada/US subgroup and supporting the role of Rd continuous as a standard of care for TNE pts with NDMM. The efficacy observed with Rd continuous raises the question on the role of immunostimulatory effects by the immunomodulatory agents in NDMM.image

Immune-related adverse events are associated with improved outcomes in ICI-treated renal cell carcinoma patients.

645 Background: With the approval of immune-checkpoint inhibitors (ICI) as first and second line agents for treating metastatic renal cell carcinoma (RCC), immune-related adverse events (irAE) are a growing concern. In this study, we present the safety profile and outcomes of 90 patients with RCC treated at two centers, including a university (UT Southwestern/Clements University Hospital) and a county hospital (UT Southwestern/Parkland). Methods: All patients with RCC treated with ICI were identified from 2013 to January 31, 2018. We examined the incidence of any treatment-related adverse events and “select” irAEs and evaluated their impact on patient outcomes and therapeutic decisions. Kaplan-Meier methods and Cox proportional hazards regression models were used to compare overall survival (OS) and time to next therapy (TTNT) by the presence of irAEs. Results: Of 90 patients treated with ICI, 65 (72.2%) patients experienced adverse events, most commonly fatigue (37.8%), nausea (14%), and decreased appetite (12.2%). Select irAEs were seen in 38 (42.2%) with the most common irAEs involving the skin (15.6%), gastrointestinal tract (14%), endocrine organs (11%), and lungs (7.8%). There were 15 (16.7%) grade III/IV irAEs resulting in cessation of therapy for 12 (13.3%) patients. The median OS was 35.9 (95% CI: 24.3-not reached) and 26.5 months (95% CI: 10.2-28.8; p = 0.002) for patients with and without irAEs, respectively. The median TTNT was 17.8 (95% CI: 11.3-29.3) and 6.6 months (95% CI: 4.5-9.6; p = 0.002) for patients with and without irAEs, respectively. In multivariate analysis of irAE status and Heng prognostic score, irAEs were associated with improved OS, HR 0.376 (95% CI 0.179–0.792; p = 0.010) and TTNT, HR 0.482 (95% CI 0.280–0.829; p = 0.008). Conclusions: ICI in RCC is well tolerated with only 16.7% of patients experiencing an adverse event resulting in cessation of therapy. The development of an irAE correlated with both an improved median OS as well as median TTNT, a benefit that persisted after multivariate analysis including Heng prognostic scoring. These findings suggest that the development of irAEs may be an independent positive prognostic factor in patients with RCC treated with ICI.

Nivolumab Treatment Beyond Investigator-Assessed Progression: Extended Follow-up in Patients with Relapsed/Refractory Classical Hodgkin Lymphoma from the Phase 2 CheckMate 205 Study

Nivolumab Treatment Beyond Investigator-Assessed Progression: Extended Follow-up in Patients with Relapsed/Refractory Classical Hodgkin Lymphoma from the Phase 2 CheckMate 205 Study

Real-World Outcomes for Transplant-Ineligible Patients with Newly Diagnosed Multiple Myeloma Treated with Lenalidomide, Bortezomib, and Dexamethasone, or Bortezomib and Dexamethasone: An Enhanced Electronic Health Records Database Analysis

Background: For transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM), the only category 1 regimens recommended by the National Comprehensive Cancer Network (NCCN) are lenalidomide and dexamethasone (Rd)-based, including triplet therapy with lenalidomide, bortezomib, and dexamethasone (RVd) (NCCN Myeloma v4.2018). Other doublet regimens, such as bortezomib and dexamethasone (Vd), are still a first-line option for patients with NDMM, especially for those who are elderly and/or frail. However, the latter population is either excluded or markedly underrepresented in clinical trials. Using an electronic health records (EHRs) database, we compared outcomes when either RVd or Vd were used in the treatment of transplant-ineligible patients with NDMM in a real-world practice setting, after adjusting for baseline demographic and clinical differences between the two cohorts.Methods: A retrospective observational study of patients with NDMM was conducted using EHRs from a nationally representative database (Flatiron Health). The Flatiron Network database is an enhanced oncology EHR database of patients treated at 265 clinics throughout the USA. Patients diagnosed with multiple myeloma, ICD-9 (203.0x) or ICD-10 (C90.xx), between January 2011 and May 2018 who were treated with RVd or Vd and did not undergo stem cell transplantation were included in the analysis. The primary comparison was time to next therapy (TTNT) in the overall population and in a subset of frail patients, as determined by a composite score based on age, Eastern Cooperative Oncology Group performance status (ECOG PS) score, and Charlson Comorbidity Index (CCI). Data regarding overall and progression-free survival (PFS) were limited as patient data prior to adoption of the Flatiron Network database were incomplete. Treatment-free interval (TFI) for patients who initiated a second-line therapy was defined as time from start of first-line to start of second-line therapy minus the duration of therapy (DOT). The Kaplan-Meier and Cox proportional hazard methods were used to calculate TTNT after adjusting for differences in patient baseline demographic and clinical characteristics.Results: Of the 8,470 transplant-ineligible patients with NDMM in the database, 2,369 were treated with either RVd (n = 1,309) or Vd (n = 1,060) and met the criteria for inclusion in this analysis. Patients treated with Vd were more likely to be older (median age 75 vs 70 years; P < 0.0001), frail (76.3% vs 65.4%; P = 0.0002), have creatinine clearance < 30 mL/min (23.9% vs 10.7%, P < 0.0001), have a higher ECOG PS score (P = 0.0031), and have International Staging System stage III disease (45.1% vs 28.8%; P < 0.0001). There were no significant differences in baseline neutropenia, anemia, or thrombocytopenia, or in median CCI. The proportion of patients with high-risk cytogenetics was lower in the Vd group (19.7% vs 26.0%; P < 0.0001).The mean DOT was longer for RVd (11.4 ± standard deviation [SD] 13.3 months) than for Vd (7.7 ± SD 9.7 months). However, the median adjusted TTNT was significantly longer with RVd than Vd (40.9 vs 14.8 months; hazard ratio [HR] 0.43; 95% confidence interval [CI] 0.33-0.55; P < 0.0001). The proportion of patients initiating a new treatment was lower in the RVd group (24.8% vs 40.6%; P < 0.0001). Among those who initiated a second-line therapy, the mean TFI for RVd compared with Vd was 42.6 versus 39.3 days, respectively (P = 0.2214).Among the 735 frail patients (416 RVd and 319 Vd), the median TTNT was significantly longer with RVd (32.6 vs 17.1 months; HR 0.40; 95% CI 0.29-0.54; P < 0.0001; Figure). Similar to the overall population, there were no significant differences in TFI (54.9 vs 29.6 days, P = 0.2598) and a significantly higher proportion of Vd patients initiated a new treatment (22.1% vs 36.4%; P < 0.001).Conclusions: In this real-world practice setting where PFS cannot be measured directly, triplet therapy with RVd significantly prolonged TTNT compared with Vd by 26.1 months in the overall patient population, and by 15.5 months in frail transplant-ineligible patients with NDMM. [Display omitted] DisclosuresChari:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnology: Membership on an entity's Board of Directors or advisory committees; The Binding Site: Consultancy; Array Biopharma: Research Funding; Bristol Myers Squibb: Consultancy. Ung:Celgene Corporation: Employment, Equity Ownership. Tian:Celgene Corporation: Employment. Agarwal:Celgene Corporation: Employment, Equity Ownership. Parikh:Celgene Corporation: Employment, Equity Ownership.

Long-Lasting Remissions for Myeloma Patients on Daratumumab Therapy from the GEN501 and GEN503 Trials

IntroductionThe first two trials to test the activity of daratumumab (DARA) in relapsed/refractory multiple myeloma (MM) were GEN501 (DARA monotherapy) and GEN503 (DARA in combination with lenalidomide [LEN] and dexamethasone [DEX]). GEN501 enrolled 104 participants from 2008 and GEN503 enrolled 45 participants from 2012. GEN501 has been completed; GEN503 is active but has finished accrual. We are reporting on ten patients that are still responding to DARA therapy, several years after their inclusion in the GEN501 and GEN503 trials.MethodsTen patients were included from three participating centers in Denmark, The Netherlands and Sweden. DARA therapy had to be continuous from the initiation of trial participation with no evidence of progressive disease. Data were collected retrospectively from patient charts. Clinical characteristics, ISS and FISH results were assessed at the time of diagnosis. Lines of myeloma therapy prior to inclusion in GEN501 or GEN503 were reviewed; duration of therapy, time to next therapy (TNT) and response to each of the prior lines of therapy were determined. Results of minimal residual disease (MRD) assessments were reviewed.ResultsTen patients (six men, four women) were identified, three from GEN501 and seven from the GEN503. Four out of seven patients in GEN503 stopped LEN and DEX treatment due to side effects, but all ten patients are still treated with DARA intravenously every four weeks.Patients were diagnosed with MM between 2005 and 2012. The median age at diagnosis was 59 years (range 49-62). Seven patients had IgG-kappa, two had kappa light-chain only and one patient had IgG-lambda M-protein. Nine patients had anemia, eight had bone disease, three had renal insufficiency and one had hypercalcemia at diagnosis. ISS was available in nine patients. Three patients had ISS I, five had ISS II and one had ISS III. FISH at diagnosis was available in eight patients; none of which had high-risk cytogenetics, defined as the presence of either del 17p, t(4;14) or t(14;16).The prior lines of therapy are summarized in Table 1. The median number of prior lines of therapy was 3 (range 1-5). Nine patients had received high-dose melphalan with autologous stem cell transplantation; one of these was a tandem autologous transplantation. All patients had been treated with bortezomib; seven patients had been treated with LEN. Three patients were refractory to bortezomib; two were refractory to LEN. The best response to any prior line of therapy was CR in three, VGPR in two, PR in four patients and PD in one patient. The median TNT was 37 months (range 2-68) for the first (n=10), 11 months (range 1-63) for the second (n=7) and 29 months (range 1-55) for the third (n=5) prior line of therapy. One patient had been treated with five prior lines of therapy; the TNT for the fourth and fifth lines were 22 months each.DARA therapy and MRD results are summarized in Table 2. Patients were enrolled in GEN501 or GEN503 between 2013 and 2015. The median time from diagnosis to the start of DARA therapy was 57 months (range 12-168). The best response to therapy was sCR in eight patients, CR in one patient and VGPR in one patient. The median duration of DARA therapy was 49 months (range 39-62). Eight of ten patients achieved a longer response to DARA therapy with or without LEN and DEX than to any previous regimen. Bone marrow MRD assessments were carried out by flow-cytometry between 2014 and 2018 in all patients. The sensitivity of the used assay was 10-6 in two, 10-5 in three and 10-4 in five patients. Eight subjects were bone marrow MRD-negative and two subjects were MRD-positive at a sensitivity of 10-4 and 10-5, respectively. Imaging MRD assessments were carried out in eight patients between 2017 and 2018. PET-CT was carried out in all eight patients; diffusion-weighted whole-body MRI was carried out in five patients. All patients were imaging MRD-negative.ConclusionsContinuous DARA treatment, either as monotherapy or combined with LEN and DEX can achieve MRD-negative disease and unprecedented long-lasting remissions in select patients with relapsed or refractory multiple myeloma in the absence of high-risk cytogenetics. [Display omitted] DisclosuresMinnema:Amgen: Consultancy; Takeda: Consultancy; Celgene: Consultancy, Research Funding; Janssen: Consultancy; Servier: Consultancy. Plesner:Celgene: Other: Independent Response Assessment Comittee; Janssen: Consultancy.

Salvage Autologous Stem Cell Transplantation in Multiple Myeloma: Investigating the Impact of Pre-Transplant Therapy

Salvage Autologous Stem Cell Transplantation in Multiple Myeloma: Investigating the Impact of Pre-Transplant Therapy

Chronic Lymphocytic Leukemia: Clinical Stages Maintain Their Prognostic Significance Over the Course of the Disease and Are Surrogates for Response to Therapy

BackgroundTo determine whether in patients with chronic lymphocytic leukemia (CLL), the clinical stage maintains prognostic significance over time and can be considered as a surrogate for the response to therapy. Patients and MethodsThe data from 229 CLL patients were retrospectively evaluated. The main aims of the study were to describe the changes in clinical stage during the course of CLL as a result of the response to treatment and to determine the time to next therapy (TTNT) and overall survival (OS) according to those changes, in particular, among the heterogeneous International Workshop on CLL (IWCLL) partial response (PR) category. ResultsAmong the patients in the IWCLL PR category, differences were found in TTNT and OS according to the clinical stage at the response evaluation. With a median follow-up period of 91 months (range, 2-390 months), patients with a PR- Binet A at the response evaluation had significantly longer TTNT and OS compared with those with PR-Binet B/C (median TTNT, 26 vs. 11 months; P = .00; median OS, 63 vs. 43 months; P = .047). ConclusionThe results of the present study have shown that for patients with CLL, the Binet clinical stages are good outcome predictors throughout the disease course and also suggest that changes in Binet clinical stage could be useful as response surrogates and to divide the IWCLL PR category into different prognostic subgroups.

Nivolumab Treatment Beyond Investigator-Assessed Progression: Outcomes in Patients with Relapsed/Refractory Classical Hodgkin Lymphoma from the Phase 2 Checkmate 205 Study

Nivolumab Treatment Beyond Investigator-Assessed Progression: Outcomes in Patients with Relapsed/Refractory Classical Hodgkin Lymphoma from the Phase 2 Checkmate 205 Study

Retrospective analysis on R‐DHAP/OX and ASCT as salvage treatment for relapsed/refractory high‐risk follicular lymphoma

Introduction: Follicular lymphoma (FL) relapsing within the first 2 years from frontline chemo-immunotherapy is associated with a median overall survival of 5 years from the time of progression, and optimal subsequent treatment remains uncertain. Rituximab, dexamethasone, high-dose cytarabine, and cisplatin/oxaliplatin (R-DHAP/Ox), followed by autologous stem cell transplant (ASCT), could be a reasonable option because it has shown efficacy in diffuse large B-cell lymphoma with germinal center subtype. Methods: We retrospectively analyzed patients with FL relapsing within 2 years after first-line chemo-immunotherapy who received subsequent R-DHAP/Ox. Exclusion criteria were histologic grade 3B and transformation to DLBCL before R-DHAP/Ox. Overall survival (OS) was calculated from risk-defining events as described in the LymphoCare study (Casulo et al. JCO 2015). Time to next therapy (TTNT) was calculated from the end of one line of therapy to start of the subsequent therapy. Survival end points were estimated with the Kaplan-Meyer method. Results: Data from 67 patients were collected, from 3 Italian institutions; 48 patients were eligible. Characteristics of the population are summarized in the table. First-line therapy was R-CHOP in 37 (77%), R-fludarabine-mitoxantrone in 4 (8.3%), R-CVP in 2 (4.1%), R-bendamustine in 2 (4.1%), R-FND, R-chlorambucil, and R-HDS (HD sequential of etoposide, cyclophosphamide, mitoxantrone, melphalan + ASCT) in 1 (2.1%). Thirty-four 34 (70.8%) patients underwent 1 line of therapy prior to R-DHAP/Ox, 11 (22.9%) underwent 2 lines of therapy, and 3 (6.3%) had 3 or more lines before R-DHAP/Ox. The median TTNT from first-line was 14.3 months (range 10.6-19.4). LymphoCare patients Early POD (n = 110) Italian patients Early POD (n = 48) Age, y Median Range 58 31-88 52 29-72 Sex Female Male 38 35 72 65 16 34 32 66 Histologic grade 1 or 2 3a Missing 63 66 33 34 14 39 81 9 19 0 FLIPI score Low, 0 to 1 Intermediate, 2 High, 3 to 5 Missing 10 12 29 34 47 54 24 8 16 15 32 24 52 1 Conclusions: In this population of high-risk, early relapsing FL, R-DHAP/Ox +/− ASCT was found to be active, with a TTNT significantly longer than that experienced following first-line therapy. This population had very similar FLIPI risk scores compared to the LymphoCare study population but appears to have experienced better survival outcomes. Late events continue to occur, and cure appears unlikely. Prospective studies of R-DHAP/Ox +/− ASCT are warranted in this high-risk FL population. Keywords: autologous stem cell transplantation (ASCT); DHAP; follicular lymphoma (FL)

Patterns of Total Costs of Care over Time for Patients with Multiple Myeloma (MM)

Introduction. A previous study of patients (pts) with newly-diagnosed multiple myeloma (NDMM) showed that initial high monthly total costs declined over time until returning near initial levels upon pts advancing to later lines of treatment (Tx) at disease progression (Arikian, CMRO 2015). However, the longer-term economic implications of the choice of first-line Tx, regardless of subsequent Tx regimens, have not been described. We utilized an intent-to-treat approach to further evaluate and compare the total costs of NDMM patient cohorts initiated on Lenalidomide (LEN) or Bortezomib (BORT)-based Tx and followed these patients over 54 months.Methods: A retrospective analysis was performed using a large US medical and pharmacy claims database, covering > 25 million commercial and Medicare lives annually. NDMM patients were defined as having ≥ 2 outpatient claims or ≥ 1 inpatient medical claim with a diagnosis of MM (ICD-9-CM code 203.0X), with the first such claim used to define the index date. Inclusion criteria required ≥ 12 months' pre-index and ≥ 6 months' post-index continuous enrollment from 2006 - 2013, and evidence of initiation of a subsequent line of therapy. Pts with claims for stem cell transplantation (SCT) or receiving concurrent LEN plus BORT as first-line Tx were excluded. The analysis focused on cohorts of NDMM pts receiving LEN or BORT-based first line Tx, who progressed to one or more subsequent lines of Tx, using time to next therapy (TTNT) as a proxy for progression. Pts receiving LEN or BORT-based first line Tx were randomly matched 1:1 on age (+/- 3 years at index), sex, baseline Charlson comorbidity score (+/- 1), and presence of renal disease. Using methods similar to those described by Gaultney(J Clin Pharm Ther, 2013), pts' average monthly costs and standard errors were determined, including medical and pharmacy costs, and total cost patterns were calculated from first line Tx initiation until the end of patient eligibility or 54 months.Results: 1,181 NDMM pts receiving LEN (N=444) or BORT-based (N=737) first line Tx with complete data available through initiation of subsequent line of Tx were identified. After matching, 856 NDMM patients remained (428 LEN, 428 BORT). Monthly total direct medical plus pharmacy costs for these pts were in excess of $12,000 at initiation. Total monthly costs declined quarterly for each cohort until the median TTNT was reached (20 months for BORT; 37 months for LEN). As increasing numbers of pts in each cohort then advanced to subsequent lines of therapy, costs of those patients began to offset continued cost declines for pts still on first line of therapy. Over the full 54 month follow-up period, total monthly costs averaged $8,324 (SE = $370.30) for pts initiated on LEN vs. $10,728 (SE = $500.55) for pts initiated on BORT (p-value <0.001). Medical costs represented 54-57% of total monthly costs for each cohort. In each cohort, the most common Tx option upon disease progression was to switch to the other regimen.Conclusions: For a matched population of NDMM pts followed continuously for 54 months, initiation on LEN- versus BORT-based Tx without SCT was associated with an average of $2,404 lower monthly direct total costs. Following initiation of first-line therapy, total monthly costs per pt declined quarterly until initiation of the next line of Tx. Cumulative costs over the 54-month period were over $120,000 lower per pt in favor of the LEN cohort, influenced by more rapid advancement to subsequent Tx in the BORT cohort, and the associated higher costs. Based on second-line Tx patterns, this analysis also suggests that a sequence of LEN in first line followed by BORT in second line is associated with lower costs over time compared to the reverse sequence. Due to the nature of retrospective claims, some underlying differences may remain between the two cohorts even after matching. [Display omitted] DisclosuresArikian:Genesis Research: Consultancy. Binder:Celgene Corporation: Employment, Equity Ownership. Gibson:Celgene Corporation: Employment, Equity Ownership. Hu:Celgene Corporation: Employment, Equity Ownership, Patents & Royalties. Nagarwala:Celgene Corporation: Employment. Hussein:Celgene Corporation: Employment, Equity Ownership. Corvino:Genesis Research LLC: Consultancy. Lee:Genesis Research LLC: Consultancy. Surinach:Genesis Research LLC: Consultancy. Kaura:Celgene Corporation: Employment. Usmani:Onyx: Consultancy, Honoraria, Research Funding; Celgene Corporation: Consultancy, Honoraria; Janssen: Research Funding.

Intention to Treat vs Age of Diagnosis. Analysis of Benefitial Effect of New Agents in the Treatment of Newly Diagnosed Multiple Myeloma (NDMM)

e258 dose-modifications to sustain control of disease while managing toxicities. Previous analysis demonstrated LEN dose-modification was associated with longer duration of therapy (DOT) and time to progression (TTP), using time to next therapy (TTNT) as a proxy. This updated analysis evaluates the effect of LEN response on that association. Methods: A retrospective analysis of a large US claims database evaluated patients with NDMM without stem cell transplant (SCT) and treated with LEN from 2006-2013. Median DOT and TTNT were compared between patients +/LEN dose-modifications (increase or decrease) and in subgroups of LEN responders, defined as receiving LEN for 4 (Responders 1) or 6 months (Responders 2). Results: Of 1281 LEN-treated patients with NDMM, 514 had 1 dose-modification. 1,031 had 4 months DOT (462 dose-modified), and 816 had DOT 6 months (401 dose-modified). A 9-12 month advantage in median DOT and TTNT for dose-modified patients was consistent across groups (p<0.01) (Table). Charlson comorbidity scores were similar in patients +/dose-modifications. Conclusions: For non-SCT patients treated with LEN for NDMM in the real-world setting, longer DOT and TTP were observed for patients experiencing dosemodifications. Most patients adhered to treatment. This analysis suggests that LEN dose-modification in NDMMmay be an effective strategy to prolong TTP, based on the proxy measure of TTNT.

Relationship Between Lenalidomide Dose Modification and Time to Next Treatment in Newly Diagnosed Multiple Myeloma Patients

Introduction: Multiple clinical studies in patients (pts) with newly diagnosed multiple myeloma (NDMM) have shown benefits from continuous lenalidomide (LEN) treatment (Tx), including extended progression-free survival (PFS), time to progression (TTP), and overall survival (OS) (Facon, Blood 2013; Palumbo, NEJM 2012). Dose modifications are commonly utilized by physicians as part of continuous Tx plans to sustain control of disease while managing toxicities. Previous analysis has shown that dose modification of LEN was associated with longer duration of therapy (DOT) relative to non-dose modification, in the real-world setting (Lang, Blood 2013). This study aimed to evaluate whether LEN dose modification is associated with a longer TTP in NDMM pts, utilizing time to next therapy (TTNT) as a proxy measure available from claims data.Methods: A retrospective study was conducted using a large US medical and pharmacy claims database, covering > 25 million lives annually. NDMM pts were identified with at least 2 outpatient claims or 1 inpatient medical claim associated with a diagnosis of MM (ICD-9-CM code 203.0X), with the first such claim used to define the index date. A minimum of 12 months’ pre-index enrollment and 6 months’ post-index continuous enrollment between Jan 1 2006 and December 31 2012 was required. The analysis focused on NDMM pts treated with LEN who did not have claims for stem cell transplantation (SCT), to avoid DOT limitations imposed by fixed-length induction Tx. Median DOT and TTNT were compared in NDMM pts with and without LEN dose modifications (dose increase or decrease). Charlson comorbidity scores were determined to compare baseline measures between the groups.Results: Of the 1,360 pts who met the inclusion criteria, 470 (35%) had LEN dose modifications, including 154 pts with at least one dose increase and 421 pts with at least one dose decrease. The majority of pts had an initial dose of 25mg. The median DOT was 447 days in pts with LEN dose modification and 182 days in those pts with no dose modification (p < 0.001). The median DOT in pts with dose modification was consistent regardless of whether they experienced a dose increase or decrease, with no significant difference. The median TTNT in pts with LEN dose modification was 3.5 yrs compared to 2.0 yrs in pts without dose modification (p < 0.001; Figure 1). Charlson comorbidity scores were similar in pts with and without LEN dose modification. [Display omitted] Conclusions: For non-SCT NDMM patients treated with LEN, dose modifications during their treatment were associated with a doubling of the median therapy duration and a 71% longer median TNTT, compared to pts without LEN dose modification. The DOT and TTNT in pts with dose modification were similar to median values reported for the LEN continuous Tx arm of the FIRST clinical trial (Facon, Blood 2013). This analysis suggests that LEN dose modification in the Tx of NDMM may be an effective tool in the real-world setting for pts to achieve sustained disease Tx and the associated prolonged time to progression, based on the proxy measure of TTNT. DisclosuresUsmani:Celgene Corporation: Consultancy, Honoraria, Research Funding; Millennium: Consultancy, Honoraria; Onyx: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy; Array BioPharma: Research Funding; Janssen: Research Funding; Pharmacyclics: Research Funding. Off Label Use: Lenalidomide in newly diagnosed multiple myeloma patients. Binder:Celgene Corporation: Employment, Equity Ownership. Milentijevic:Celgene Corporation: Consultancy. Hu:Celgene: Employment. Nagarwala:Celgene Corporation: Employment. Corvino:Genesis Research LLC: Consultancy. Arikian:Genesis Research: Consultancy. Surinach:Genesis Research LLC: Consultancy. Harwin:Celgene Corporation: Honoraria.

Efficacy and Safety Of Three Bortezomib-Based Induction and Maintenance Regimens In Previously Untreated, Transplant-Ineligible Multiple Myeloma (MM) Patients (Pts): Final Results From The Randomized, Phase 3b, US Community-Based UPFRONT Study (NCT00507416)

Efficacy and Safety Of Three Bortezomib-Based Induction and Maintenance Regimens In Previously Untreated, Transplant-Ineligible Multiple Myeloma (MM) Patients (Pts): Final Results From The Randomized, Phase 3b, US Community-Based UPFRONT Study (NCT00507416)

Bortezomib in patients with relapsed or refractory mantle cell lymphoma: updated time-to-event analyses of the multicenter phase 2 PINNACLE study

BackgroundWe previously reported results of the phase 2, multicenter PINNACLE study, which confirmed the substantial single-agent activity of bortezomib in patients with relapsed or refractory mantle cell lymphoma (MCL). Materials and methodsWe report updated time-to-event data, in all patients and by response to treatment, after extended follow-up (median 26.4 months). ResultsMedian time to progression (TTP) was 6.7 months. Median time to next therapy (TTNT) was 7.4 months. Median overall survival (OS) was 23.5 months. In responding patients, median TTP was 12.4 months, median duration of response (DOR) was 9.2 months, median TTNT was 14.3 months, and median OS was 35.4 months. Patients achieving complete response had heterogeneous disease characteristics; among these patients, median TTP and DOR were not reached, and median OS was 36.0 months. One-year survival rate was 69% overall and 91% in responding patients. Median OS from diagnosis was 61.1 months, after median follow-up of 63.7 months. Activity was seen in patients with refractory disease and patients relapsing following high-intensity treatment. Toxicity was generally manageable. ConclusionsSingle-agent bortezomib is associated with lengthy responses and notable survival in patients with relapsed or refractory MCL, with considerable TTP and TTNT in responding patients, suggesting substantial clinical benefit.