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Srinivasan, Shankar

https://orcid.org/0000-0002-5843-7008

Mayo Clinic

Bristol-Myers Squibb (United States)

Citations 11

Effect of initial treatment on health‐related quality of life in patients with newly diagnosed multiple myeloma without immediate stem cell transplant intent: results from the Connect® MM Registry
Abonour, Rafat , Rifkin, Robert M. , Gasparetto, Cristina , Toomey, Kathleen, Durie, Brian G.M. , Terebelo, Howard R. , Narang, Mohit , Ailawadhi, Sikander , Omel, James, Srinivasan, Shankar , Kitali, Amani, Agarwal, Amit , Investigators, the CONNECT MM Registry, Terebelo, Howard R , Ailawadhi, Sikander , Hardin, James W. , Jagannath, Sundar , Lee, Hans C. , Wagner, Lynne I. , Investigators, the CONNECT MM Registry

British Journal of Haematology | October 29, 2020 | Volume: 193 | Issue: 1 | Pages: 93-100

10.1111/bjh.17131 Get It

SummaryAlthough new multiple myeloma (MM) therapies are effective in alleviating some disease‐associated symptoms (e.g. bone pain, fatigue, functional decline), they can result in additional toxicities, further impacting health‐related quality of life (HRQoL). Here, we compared HRQoL and safety of lenalidomide‐bortezomib‐dexamethasone [RVd (n = 445)], bortezomib‐melphalan‐prednisone [VMP (n = 77)] and Vd or VMP (n = 588) in patients with newly diagnosed MM (NDMM) from the Connect® MM Registry, a large, USA, multicentre, prospective observational cohort study. Functional Assessment of Cancer Therapy‐Multiple Myeloma subscale, EuroQol‐5D overall score and Bone Pain Inventory HRQoL scores were significantly improved with RVd versus Vd/VMP. Serious adverse event rates were similar in all groups. Treatment with RVd maintained HRQoL in this real‐world, largely community‐based population of patients with NDMM.
Continuous lenalidomide and low‐dose dexamethasone in patients with transplant‐ineligible newly diagnosed MM: FIRST trial subanalysis of Canadian/US patients
Belch, Andrew R. , White, Darrell , Cheung, Matthew C. , Chen, Christine , Shustik, Chaim, Song, Kevin , Tosikyan, Axel, Brown, Diane , Robinson, Suzanne, Srinivasan, Shankar , Belch, Andrew , Cheung, Matthew , Bahlis, Nizar Jacques , Dispenzieri, Angela , Anderson, Kenneth C. , Facon, Thierry T.F.

Cancer Medicine | October 13, 2020 | Volume: 9 | Issue: 23 | Pages: 8923-8930

10.1002/cam4.3511 Get It

AbstractThe phase 3 FIRST trial demonstrated significant improvement in progression‐free survival (PFS) and overall survival (OS) with an immune‐stimulatory agent, lenalidomide, in combination with low‐dose dexamethasone until disease progression (Rd continuous) vs melphalan +prednisone + thalidomide (MPT) in transplant‐ineligible patients with newly diagnosed multiple myeloma (NDMM). Rd continuous similarly extended PFS vs fixed‐duration Rd for 18 cycles (Rd18). Outcomes in the Canadian/US subgroup (104 patients per arm) are reported in this analysis. Rd continuous demonstrated a significant improvement in PFS vs MPT (median, 29.3 vs 20.2 months; HR, 0.69 [95% CI, 0.49‐0.97]; p = 0.03326) and an improvement vs Rd18 (median, 21.9 months). Median OS was 56.9 vs 46.8 months with Rd continuous vs MPT (p = 0.15346) and 59.5 months with Rd18. The overall response rate was higher with Rd continuous and Rd18 (78.8% and 79.8%) vs MPT (65.4%). In the 49.0%, 52.9%, and 29.8% of patients with at least very good partial response in the Rd continuous, Rd18, and MPT arms, respectively, the median PFS was 56.0, 30.9, and 40.2 months, respectively. The most common grade 3/4 treatment‐emergent adverse events were neutropenia (28.4%, 30.1%, and 52.0%), anemia (23.5%, 21.4%, and 23.5%), and infections (37.3%, 30.1%, and 24.5%) with Rd continuous, Rd18, and MPT, respectively. These results were consistent with those in the intent‐to‐treat population, confirming the benefit of Rd continuous vs MPT in the Canadian/US subgroup and supporting the role of Rd continuous as a standard of care for transplant‐ineligible patients with NDMM.
Impact of lenalidomide-bortezomib-dexamethasone (RVd) induction on patients with newly diagnosed multiple myeloma and renal impairment: Results from the Connect MM Registry.
Lee, Hans Chulhee, Omel, Jim, Toomey, Kathleen, Gasparetto, Cristina , Rifkin, Robert M. , Durie, Brian G.M. , Narang, Mohit , Terebelo, Howard R. , Dhalla, Mazaher, Mia, HE, Srinivasan, Shankar , Robinson, Suzanne, Abonour, Rafat , Ailawadhi, Sikander , Lee, Hans C. , Hardin, James W. , Jagannath, Sundar , Wagner, Lynne I. , Joshi, Prashant Ramesh

Journal of Clinical Oncology | May 25, 2020 | Volume: 38 | Issue: 15_suppl | Pages: 8518-8518

10.1200/jco.2020.38.15_suppl.8518 Get It

8518 Background: Patients (pts) with newly diagnosed multiple myeloma (NDMM) and renal impairment (RI) are often excluded from clinical trials. Data are limited on the effects of induction treatment in these pts, who may also be ineligible for autologous stem cell transplant (SCT) due to severity of RI. This analysis investigated the impact of RVd induction on renal function in transplant eligible (TE) and noneligible (TNE) pts from the Connect MM Registry, a US, multicenter, prospective, observational study. Methods: Eligible pts were ≥ 18 y and had symptomatic MM diagnosed ≤ 2 mos prior to enrollment, as defined by the International Myeloma Working Group criteria. For this analysis, pts that received front-line RVd for ≥ 3 cycles were grouped per transplant eligibility and renal function at baseline (BL; creatinine clearance [CrCl] < 30, 30-50, > 50-80, and > 80). Pts with progressive disease at BL were excluded. Renal function at 3 mos was measured. Median unadjusted progression-free survival (PFS) was calculated from start of regimen in TE and TNE populations, with pts grouped by CrCl (≤ 60 or > 60) at BL. Results: As of 7/23/19, 421 TE and 212 TNE pts received RVd for ≥ 3 cycles. TE and TNE pts were grouped by BL CrCl of < 30 (20 and 16 pts), 30-50 (36 and 50 pts), > 50-80 (117 and 63 pts), and > 80 (248 and 83 pts). Renal function improvement was observed in all pts receiving RVd, including those with moderate (30-50 CrCl) and severe (< 30 CrCl) RI at BL (Table). In pts with > 60 CrCl and ≤ 60 CrCl at BL, median PFS in TE pts was 48.6 mos and 43.2 mos, respectively. In TNE pts, median PFS was 36.4 mos and 30.6 mos, respectively. Conclusions: The results from the Connect MM Registry indicate that pts with NDMM and RI (including moderate and severe) who receive front-line RVd for ≥ 3 cycles may see improvement in renal function at 3 mos, regardless of transplant eligibility. RVd therefore can potentially be used in pts with RI. This analysis provides real-world data that support further investigation of RVd treatment in pts with moderate or severe RI. Clinical trial information: NCT01081028 . [Table: see text]
Effect of t(11;14) on outcomes of patients (pts) with newly diagnosed multiple myeloma (NDMM) in the connect MM registry.
Gasparetto, Cristina, Rifkin, Robert M. , Durie, Brian G.M. , Narang, Mohit , Terebelo, Howard R. , Toomey, Kathleen, Omel, James, Lee, Hans Chulhee, Srinivasan, Shankar , Dhalla, Mazaher, Catamero, Donna, Agarwal, Amit , Abonour, Rafat , Gasparetto, Cristina , Jagannath, Sundar , Hardin, James W. , Wagner, Lynne I. , Ailawadhi, Sikander , Lee, Hans C.

Journal of Clinical Oncology | March 12, 2020 | Volume: 37 | Issue: 15_suppl | Pages: 8032-8032

10.1200/jco.2019.37.15_suppl.8032 Get It

8032 Background: The impact of t(11;14) (16%–24% of MM pts) on prognosis is not fully understood. Consensus is lacking on the effects of induction treatment (tx) on outcomes with t(11;14). The Connect MM Registry (NCT01081028) is a large, US, multicenter, prospective observational cohort study of pts with NDMM designed to examine real-world diagnostic patterns, treatment (tx) patterns, clinical outcomes, and HRQoL pt-reported outcomes in pts with NDMM. The impact of t(11;14) on tx outcomes are reported. Methods: Analysis included data from pts from 250 community, academic, and government sites in cohort (C) 1 (9/2009–12/2011) and C2 (12/2012–4/2016), who completed first-line (1L; induction) tx and were tested for t(11;14) by FISH or cytogenetics. Primary end points (progression-free survival [PFS] and overall survival [OS]) were measured from start of 1L tx to earliest event (PFS, death or progression; OS, death), loss to follow-up, or data cutoff, adjusted for baseline (BL) risk factors. A sensitivity analysis excluding pts with concomitant cytogenetic abnormalities [del 17p, t(4;14), t(14;16), 1q+] was also performed. Results: By 1/2018, 3011 pts were enrolled; 2938 were treated. Of 1574 enrolled pts tested for t(11;14), 378 were t(11;14)+ and 1196 were t(11;14)−. More pts in C2 vs C1 were t(11;14)+ (60% vs 40%). BL characteristics were similar between groups. t(11;14) status did not affect PFS ( P= NS) or OS ( P= NS; Table). Pts in C1 and C2 received similar 1L txs (IMiD agent + proteasome inhibitor [PI], 30% vs 42%; PI only, 42% vs 43%; IMiD agent only, 17% vs 11%). Results were similar when pts with concomitant abnormalities were excluded. Conclusions: Results of this analysis suggest that t(11;14) does not affect PFS and OS outcomes in NDMM pts. Clinical trial information: NCT01081028. [Table: see text]
Connect MM: The multiple myeloma (MM) disease registry—Incidence of second primary malignancies (SPM).
Rifkin, Robert M. , Abonour, Rafat , Gasparetto, Cristina , Mehta, Jayesh, Narang, Mohit , Thomas, Sachdev , Shah, Jatin J., Terebelo, Howard R. , Toomey, Kathleen, Minton, Neil, Srinivasan, Shankar , Street, Thomas K., Sullivan, Kristen , Durie, Brian G.M. , Fonseca, Rafaël , Pashos, Chris Leo

Journal of Clinical Oncology | March 11, 2020 | Volume: 30 | Issue: 15_suppl | Pages: 8037-8037

10.1200/jco.2012.30.15_suppl.8037 Get It

8037 Background: Advances in the treatment of MM have greatly improved clinical outcomes for patients (pts). SPM occurrence has been observed in early and late stage MM as well as with increasing age. US SEER Cancer Registry reports a background incidence rate of SPM 2.1/100 person-yrs (PY) among persons ≥ 65 yrs of age. However, incidence of SPM in MM pts and the relationship to therapy still warrants further exploration. Methods: Connect MM is a US-based observational registry designed to characterize pts with newly diagnosed MM from 266 US sites. Initiated in Sep 2009, patient data were collected at baseline and each subsequent quarter with a standardized form. On Dec 14, 2011, Connect MM reached full enrollment at 1,500 pts. Results: As of Jan 13, 2012, preliminary retrospective SPM data is available for 1015 pts. Median age was 67 yrs, 56.8% male, and median follow-up was 10.6 mo (0.03-24.9 mo). 12 pts (7 male) with median age of 68.5 yrs developed SPM. Median time to SPM was 8.5 mo (0.8-17.7 mo) after treatment initiation. 11 invasive SPM were observed - 4 hematological (heme): 1 AML, 1 MDS, 1 CMML and 1 DLBCL, and 7 solid: 2 melanoma skin, 1 bronchus, 1 breast, 1 prostate, 1 tonsil, and 1 gastric carcinoid. Also, 1 pt had non-melanoma skin cancer (NMSC), and 1 pt with invasive skin cancer also had NMSC. Of the 4 pts developing heme SPM, 3 had bortezomib (BORT), 1 had thalidomide (THAL), 1 had lenalidomide (LEN), 2 had melphalan (MEL), and all 4 pts had steroids. Of the 7 pts who developed solid tumor SPM, 5 had BORT, 5 had LEN, 2 had doxorubicin, 1 had MEL, 5 had steroids, 1 had irradiation, and 1 had not received MM treatment. 2 pts with prior history of invasive malignancy developed solid tumor SPM (1 pt also developed NMSC).1 pt who received irradiation developed NMSC. Early overall incidence of invasive SPM was 1.21/100 PY (95% CI 0.60, 2.16) for all pts and 1.20/100 PY (95% CI 0.44,2.62) for pts ≥ 65 yrs of age. Conclusions: This preliminary analysis shows that SPM occurred at an expected rate in this disease specific registry of patients with NDMM and appeared to occur irrespective of MM treatment administered. Incidence rates of SPM may increase over time as patients receive transplantation and alkylators. Prospective observation will continue.
Treatment Patterns and Outcomes in Elderly Patients with Newly Diagnosed Multiple Myeloma: Results from the Connect® MM Registry
Gasparetto, Cristina, Rifkin, Robert M. , Durie, Brian G.M. , Narang, Mohit , Terebelo, Howard R. , Toomey, Kathleen, Omel, James, Srinivasan, Shankar , Dhalla, Mazaher, Agarwal, Amit , Abonour, Rafat , Lee, Hans C. , Ailawadhi, Sikander , Gasparetto, Cristina , Jagannath, Sundar , Hardin, James W. , Wagner, Lynne I. , Liu, Liang

Blood | November 16, 2019 | Volume: 134 | Issue: Supplement_1 | Pages: 3129-3129

10.1182/blood-2019-126205 Get It

Background: Multiple myeloma (MM) is common among the elderly, with 35% of patients (pts) diagnosed being aged ≥75 years (y). With increasing overall life expectancy, the incidence and prevalence of newly diagnosed and previously treated MM patients ≥80 y is expected to increase over time. Because elderly pts are often excluded from clinical trials, data focused on their treatment patterns and clinical outcomes are lacking. The Connect® MM Registry (NCT01081028) is a large, US, multicenter, prospective observational cohort study of pts with newly diagnosed MM (NDMM) designed to examine real-world diagnostic patterns, treatment patterns, clinical outcomes, and health-related quality of life patient-reported outcomes. This analysis reviews treatment patterns and outcomes in elderly pts from the Connect MM Registry. Methods: Pts enrolled in the Connect MM registry at 250 community, academic, and government sites were included in this analysis. Eligible pts were adults aged ≥18 y with symptomatic MM diagnosed ≤2 months before enrollment, as defined by International Myeloma Working Group criteria; no exclusion criteria were applied. For this analysis, pts were categorized into 4 age groups: <65, 65 to 74, 75 to 84, and ≥85 y. Pts were followed from time of enrollment to the earliest of disease progression (or death), loss to follow-up, or data cutoff date of February 7, 2019. Descriptive statistics were used for baseline characteristics and treatment regimens. Survival outcomes were analyzed using Cox regression. Time to progression (TTP) analysis excluded causes of death not related to MM. Results: Of 3011 pts enrolled (median age 67 y), 132 (4%) were aged ≥85 y, and 615 (20%) were aged 75-84 y at baseline. More pts aged ≥85 y had poor prognostic factors such as ISS stage III disease and reduced hemoglobin (<10 g/dL or >2 g/dL <LLN) compared with other age groups, although no notable differences between creatinine and calcium levels were observed across age groups (Table). A lower proportion of elderly pts (75-84 and ≥85 y) received triplet regimens as frontline therapy. More elderly pts received a single novel agent, whereas use of 2 novel agents was more common in younger pts (Table). The most common frontline regimens among elderly pts were bortezomib (V) + dexamethasone (D), followed by lenalidomide (R) + D, whereas those among younger pts included RVD, followed by VD and CyBorD (Table). No pt aged ≥85 y, and 4% of pts aged 75-84 y received high-dose chemotherapy and autologous stem cell transplant (vs 61% in the <65 y and 37% in the 65-74 y age group). The most common maintenance therapy was RD in pts ≥85 y (although the use was low) and R alone in other age groups (Table). In the ≥85 y group, 27%, 10%, and 4% of pts entered 2L, 3L, and 4L treatments respectively, vs 43%, 23%, and 13% in the <65 y group. Progression-free survival was significantly shorter in the ≥85 y age group vs the 75-84 y age group (P=0.003), 65-74 y age group (P<0.001), and <65 y age group (P<0.001; Fig.1). TTP was significantly shorter in the ≥85 y group vs the <65 y group (P=0.020); however, TTP was similar among the 65-74 y, 75-84 y, and ≥85 y cohorts (Fig. 2). Overall survival was significantly shorter in the ≥85 y group vs the 75-84 y, 65-74 y, and <65 y groups (all P<0.001; Fig. 3). The mortality rate was lowest (46%) during first-line treatment (1L) in pts aged ≥85 y (mainly attributed to MM progression) and increased in 2L and 3L (47% and 54%, respectively); a similar trend was observed in the younger age groups. The main cause of death was MM progression (29% in the ≥85 y vs 16% in the <65 y group). Other notable causes of death in the ≥85 y group included cardiac failure (5% vs 2% in <65 y group) and pneumonia (5% vs 1% in <65 y group). Conclusions: In this analysis, elderly pts received similar types of frontline and maintenance regimens as younger pts, although proportions varied with decreased use of triplet regimens with age. Considering similarities in TTP across the 65-74 y, 75-84 y, and ≥85 y cohorts, these real-world data support active treatment and aggressive supportive care of elderly symptomatic pts, including with novel agents. Additionally, further clinical studies specific to elderly patients with MM should be explored. Disclosures Lee: Amgen: Consultancy, Research Funding; GlaxoSmithKline plc: Research Funding; Sanofi: Consultancy; Daiichi Sankyo: Research Funding; Celgene: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding. Ailawadhi:Janssen: Consultancy, Research Funding; Takeda: Consultancy; Pharmacyclics: Research Funding; Amgen: Consultancy, Research Funding; Celgene: Consultancy; Cellectar: Research Funding. Gasparetto:Celgene: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; Janssen: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; BMS: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed . Jagannath:AbbVie: Consultancy; Merck & Co.: Consultancy; Bristol-Myers Squibb: Consultancy; Karyopharm Therapeutics: Consultancy; Celgene Corporation: Consultancy; Janssen Pharmaceuticals: Consultancy. Rifkin:Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees. Durie:Amgen, Celgene, Johnson & Johnson, and Takeda: Consultancy. Narang:Celgene: Speakers Bureau. Terebelo:Celgene: Honoraria; Jannsen: Speakers Bureau; Newland Medical Asociates: Employment. Toomey:Celgene: Consultancy. Hardin:Celgene: Membership on an entity's Board of Directors or advisory committees. Wagner:Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; American Cancer Society: Other: Section editor, Cancer journal. Omel:Celgene, Takeda, Janssen: Other: Patient Advisory Committees. Srinivasan:Celgene: Employment, Equity Ownership. Liu:TechData: Consultancy. Dhalla:Celgene: Employment. Agarwal:Celgene Corporation: Employment, Equity Ownership. Abonour:BMS: Consultancy; Celgene: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding.
Clinical Outcomes and Health-Related Quality of Life (HRQoL) Among Randomized Clinical Trial (RCT)-Eligible and RCT-Ineligible Patients: Results from the Connect® MM Registry
Toomey, Kathleen, Gasparetto, Cristina, Durie, Brian G.M. , Narang, Mohit , Rifkin, Robert M. , Terebelo, Howard R. , Omel, James, Srinivasan, Shankar , Dhalla, Mazaher, Catamero, Donna, Abonour, Rafat , Wagner, Lynne I. , Ailawadhi, Sikander , Jagannath, Sundar , Gasparetto, Cristina , Hardin, James W. , Lee, Hans C. , Liu, Liang

Blood | November 14, 2019 | Volume: 134 | Issue: Supplement_1 | Pages: 1843-1843

10.1182/blood-2019-126143 Get It

Background: MM clinical trials often have stringent eligibility criteria that limit the enrollment of patients (pts) reflective of the general patient population (Shah, Clin Lymphoma Myeloma Leuk 2017). The Connect® MM Registry, a prospective observational study of pts with newly diagnosed MM (NDMM) in the US, provided the opportunity to examine differences between pts with MM who were identified as RCT-eligible vs -ineligible, to observe the generalizability of clinical trial results to real-world clinical settings. Differences in baseline characteristics, treatment, clinical outcomes, and HRQoL were examined in RCT-eligible and -ineligible pts from this registry, which represents an unselected, broad real-world population. Methods: Pts with NDMM were enrolled at 250 community, academic, and government sites. Eligible pts were ≥18 y of age with symptomatic MM diagnosed ≤2 months preenrollment per the International Myeloma Working Group (IMWG) criteria. For this analysis, pts were considered ineligible for RCT per the following key exclusion criteria previously described: absolute neutrophil count ≤1.5 × 109/L, platelet count ≤75 × 109/L, creatinine >2.5 mg/dL, AST/ALT >3 times the ULN, peripheral neuropathy grade >2; ECOG PS 3/4; history of myelodysplastic syndromes/other hematologic malignancies, or solid tumors (Shah 2017). Sites administered pt HRQoL questionnaires and provided clinical data at baseline and quarterly during follow-up until death or study discontinuation. Differences in HRQoL at baseline, changes from baseline to 1 and 2 years, and survival outcomes, adjusted for covariates via propensity score, were compared between RCT-eligible/-ineligible pts. Results: Of the 3011 pts enrolled, 2873 pts met the CRAB (hyperCalcemia, Renal failure, Anemia, and Bone disease) criteria per IMWG at enrollment. Of these, 1622 (56.5%) were identified as RCT-eligible and 1251 (43.5%) as RCT-ineligible (data cut-off February 7, 2019). Both groups were similar in median age, sex, race, and ethnicity distribution, although the RCT-ineligible group had more pts aged ≥75 y (26.3% vs 23.2%) and more pts with ECOG PS 3/4 (6.2% vs none). Overall, 34.5% of RCT-ineligible pts received a transplant vs 42.8% of RCT-eligible pts. More RCT-ineligible pts had ISS stage III disease (39.4% vs 19.8%), elevated calcium (≥11.5 mg/dL; 12.7% vs 6.8%), elevated creatinine (>2.0 mg/dL; 40.3% vs 6.5%), and low hemoglobin (<10 g/dL or >2 g/dL <LLN; 60.8% vs 40.3%). Use of triplet treatment (54.2% vs 56.2%) and alkylator (24.9% vs 20.1%) was similar between the RCT-ineligible/-eligible groups. Lenalidomide + bortezomib + dexamethasone (RVd) was the most common initial therapy, and R was the most common maintenance therapy in both groups, but fewer RCT-ineligible pts received RVd as initial therapy (23.9% vs 31.0%) and R as first maintenance regimen (18.1% vs 22.7%). Absolute baseline HRQoL scores were significantly higher, indicating better HRQoL, in RCT-eligible (115.9) vs -ineligible (111.5) pts on the Functional Assessment of Cancer Therapy-Multiple Myeloma (FACT-MM) Total score (P=0.007), FACT-MM Trial Outcome Index (74.3 vs 70.3, P=0.002), and FACT-MM Subscale (37.3 vs 35.5, P=0.003). Scores were similar for EuroQol-5D Overall Index (0.73 vs 0.72, P=0.5) and Brief Pain Inventory (3.42 vs 3.43, P=0.9). Both RCT-eligible and -ineligible pts showed significant improvement in HRQoL from baseline at years 1 and 2, although the magnitude of improvement was similar between both groups (Fig. 1a and b). RCT-ineligible pts showed significantly shorter median PFS and OS vs RCT-eligible pts (Fig. 2 & 3, respectively). Conclusions: The CONNECT MM registry provided the opportunity to examine key differences between RCT-eligible and -ineligible pts. By applying common RCT eligibility criteria, a substantial proportion of MM pts (43.5%) in this real-world population may have been ineligible to participate in a RCT. RCT-ineligible pts had advanced disease, poor performance status, and poor laboratory parameters at baseline vs RCT-eligible pts, which could affect PFS and OS. These findings enhance our understanding of HRQoL among MM pts, which at present, is largely based on RCT participants. A similar magnitude of HRQoL improvement in both groups at 1 and 2 years suggests the need to evaluate RCT eligibility criteria in MM to help broaden enrollment and maximize external validity. Disclosures Wagner: Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; American Cancer Society: Other: Section editor, Cancer journal. Toomey:Celgene: Consultancy. Ailawadhi:Takeda: Consultancy; Amgen: Consultancy, Research Funding; Celgene: Consultancy; Cellectar: Research Funding; Janssen: Consultancy, Research Funding; Pharmacyclics: Research Funding. Jagannath:Merck & Co.: Consultancy; Bristol-Myers Squibb: Consultancy; AbbVie: Consultancy; Celgene Corporation: Consultancy; Janssen Pharmaceuticals: Consultancy; Karyopharm Therapeutics: Consultancy. Gasparetto:Janssen: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; BMS: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed ; Celgene: Consultancy, Honoraria, Other: Travel, accommodations, or other expenses paid or reimbursed . Durie:Amgen, Celgene, Johnson & Johnson, and Takeda: Consultancy. Narang:Celgene: Speakers Bureau. Rifkin:Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Terebelo:Celgene: Honoraria; Jannsen: Speakers Bureau; Newland Medical Asociates: Employment. Omel:Celgene, Takeda, Janssen: Other: Patient Advisory Committees. Hardin:Celgene: Membership on an entity's Board of Directors or advisory committees. Lee:Janssen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Daiichi Sankyo: Research Funding; Celgene: Consultancy, Research Funding; Sanofi: Consultancy; GlaxoSmithKline plc: Research Funding; Amgen: Consultancy, Research Funding. Srinivasan:Celgene: Employment, Equity Ownership. Liu:TechData: Consultancy. Dhalla:Celgene: Employment. Catamero:Celgene: Employment, Equity Ownership. Abonour:BMS: Consultancy; Takeda: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding.
Treatment Choices and Outcomes for Patients with Multiple Myeloma after Relapse on Lenalidomide Maintenance Therapy: Results from the Connect® MM Registry
Narang, Mohit , Rifkin, Robert M. , Terebelo, Howard R. , Toomey, Kathleen, Durie, Brian G.M. , Gasparetto, Cristina, Omel, James, Srinivasan, Shankar , Kitali, Amani, Agarwal, Amit , Abonour, Rafat , Jagannath, Sundar , Ailawadhi, Sikander , Hardin, James W. , Gasparetto, Cristina , Wagner, Lynne I.

Blood | October 14, 2019 | Volume: 132 | Issue: Supplement 1 | Pages: 3232-3232

10.1182/blood-2018-99-110877 Get It

Abstract Background : Treatment for relapsed multiple myeloma (MM) has evolved with the availability of many novel agents; outcomes in patients with newly diagnosed MM have improved with IMiD® agents (lenalidomide [R] or pomalidomide) and proteasome inhibitor (PI) use. Regardless of autologous stem cell transplant, many patients receive R maintenance therapy (Jagannath, Blood Adv 2018; Palumbo, N Engl J Med 2012). However, there is a lack of data describing the nature of relapse and treatment choices for patients progressing on R maintenance therapy. Recent phase III data do not evaluate these patients who are relapsed or refractory to R; current treatment guidelines do not specifically recommend second-line (2L) treatment options for these patients (Laubach, Leukemia 2016). However, phase III data show that pomalidomide in combination with bortezomib and dexamethasone improves progression-free survival (PFS) (HR 0.54; P = 0.0027) in R-exposed and refractory patients, including those with 1 prior line (Richardson, J Clin Oncol 2018). The Connect MM Registry is a US, multicenter, prospective observational cohort study designed to examine diagnostic and treatment patterns, clinical outcomes and quality of life in patients with MM. For patients who received R maintenance therapy, we describe patterns of relapse, 2L treatment choice, and outcomes. Methods : From 250 sites, transplant eligible and ineligible adult patients ≤ 60 days from MM diagnosis were enrolled (N = 3011). Patients were treated at physicians' discretion and followed up for treatment and outcomes until early discontinuation or study end. Patients who relapsed during R maintenance therapy (≤ 15 mg; assessed by treating physician), were analyzed for baseline (BL) characteristics, nature of relapse, and 2L treatment. Patients with symptoms at time of relapse were defined as the presence of ≥ 1 CRAB (hyperCalcemia, Renal failure, Anemia, and Bone disease) criterion ± 60 d from PD; absence of CRAB criteria at PD in this window was considered nonsymptomatic relapse. Primary endpoint was PFS from start of 2L; safety (serious adverse events; SAE) from start of 2L was also assessed. Logistic regression analyses on all BL factors and factors before start of 2L treatment were performed to determine covariates differentiating comparator groups. Survival outcomes were analyzed using a Cox regression after adjusting for covariates. Results : Data cutoff: 1/15/18. Of 2938 treated patients, 1102 entered 2L, 236 having received R maintenance therapy in 1L. Of those patients, 52% (n = 123) and 47% (n = 112) experienced symptoms at time of relapse and nonsymptomatic relapse, respectively (data not available for 1 patient). The top ten 2L regimens are presented in the Table. Median duration of prior maintenance therapy (367 d [IQR: 577] vs 489 d [IQR: 599]) and time from first progression to start of 2L treatment (0.3 vs 0.3 mo) did not notably differ between nature of relapse groups. Prolonged median PFS from start of 2L was observed for patients receiving triplet+ (≥ 3 agents) vs doublet (≤ 2 agents) regimens (HR: 0.72; Figure 1). PFS was better for IMiD agent + PI group compared with PI (without IMiD agents) group (HR, 0.68; Figure 2). Results of sensitivity analyses and overall survival will be presented. SAEs occurred similarly among treatment groups: 42.6% with IMiD agent + PI, 34.5% with IMiD agent (without PI), and 35.8% with PI. Conclusions: This is the first description of relapse patterns, 2L treatment choice and survival outcomes after PD on R maintenance therapy in community-based patients. Nearly equal numbers of patients had symptoms at time of relapse and nonsymptomatic relapse on R maintenance therapy. After PD on R maintenance, approximately 50% of patients switched to PI regimens without IMiD agents, 25% continued with IMiD agent + PI regimens, and 25% continued in the IMiD agents group. Our data show PFS benefit for triplet+ over doublet treatment in 2L. Patients in the IMiD agent + PI group gained survival benefits over patients in the PI group. Further characterization of the patients continuing with IMiD treatment in 2L after R maintenance therapy relapse (~ 25% of patients) are ongoing. Follow-up with recently approved agents (elotuzumab, daratumumab) and their use in 2L is limited in this analysis. These data may be used to better inform treatment choices after relapse on R maintenance therapy. Disclosures Jagannath: Celgene: Consultancy; Merck: Consultancy; Multiple Myeloma Research Foundation: Speakers Bureau; Medicom: Speakers Bureau; Bristol-Myers Squibb: Consultancy; Novartis: Consultancy. Narang:Janssen: Speakers Bureau; Celgene: Consultancy, Speakers Bureau. Ailawadhi:Takeda: Consultancy; Amgen: Consultancy; Janssen: Consultancy; Pharmacyclics: Research Funding; Celgene: Consultancy. Rifkin:Celgene: Consultancy; Boehringer Ingelheim: Consultancy; McKesson: Equity Ownership; EMD Serono: Consultancy; Amgen: Consultancy; Takeda: Consultancy; Sandoz: Consultancy. Terebelo:Celgene: Consultancy; Janssen: Speakers Bureau; Takeda: Speakers Bureau; Pharmacyclics: Speakers Bureau. Toomey:Celgene: Consultancy; Myriad Genetics: Speakers Bureau; Dava Oncology: Other: Travel. Durie:Takeda: Consultancy; Janssen: Consultancy; Celgene: Consultancy; Amgen: Consultancy. Hardin:Celgene: Consultancy. Gasparetto:Janssen: Consultancy, Honoraria, Other: Travel; Bristol-Myers Squibb: Consultancy, Honoraria, Other: Travel; Takeda: Honoraria; Celgene: Consultancy, Honoraria, Other: Travel, Research Funding. Wagner:EveryFit: Consultancy; Gilead: Consultancy; Janssen: Consultancy. Omel:Takeda Oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees. Srinivasan:Celgene: Employment. Kitali:Celgene: Employment. Agarwal:Celgene Corporation: Employment, Equity Ownership. Abonour:Prothena: Research Funding; Takeda: Consultancy, Research Funding; Celgene: Consultancy, Research Funding.
Treatment (tx) journeys in newly diagnosed multiple myeloma (NDMM) patients (pts): Results from the Connect MM Registry.
Rifkin, Robert M. , Gasparetto, Cristina, Toomey, Kathleen, Durie, Brian G.M. , Terebelo, Howard R. , Narang, Mohit , Srinivasan, Shankar , YoussefAgha, Ahmed, Ung, Brian , Kitali, Amani, Flick, E. Dawn, Agarwal, Amit , Abonour, Rafat , Jagannath, Sundar , Gasparetto, Cristina , Hardin, James W. , Wagner, Lynne I. , Ailawadhi, Sikander

Journal of Clinical Oncology | September 5, 2018 | Volume: 36 | Issue: 15_suppl | Pages: 8041-8041

10.1200/jco.2018.36.15_suppl.8041 Get It

Predictors of long-term survival in newly diagnosed multiple myeloma (NDMM) patients (pts) enrolled in the Connect MM registry.
Gasparetto, Cristina, Rifkin, Robert M. , Terebelo, Howard R. , Toomey, Kathleen, Durie, Brian G.M. , Narang, Mohit , Flick, E. Dawn, Kotey, Stanley, Srinivasan, Shankar , Kitali, Amani, Agarwal, Amit , Abonour, Rafat , Gasparetto, Cristina , Hardin, James W. , Jagannath, Sundar , Wagner, Lynne I. , Ailawadhi, Sikander

Journal of Clinical Oncology | September 5, 2018 | Volume: 36 | Issue: 15_suppl | Pages: 8037-8037

10.1200/jco.2018.36.15_suppl.8037 Get It