Abstract: The treatment of multiple myeloma has dramatically improved due to the availability of novel therapies that are highly effective and are quickly moving into first-line therapy. The Canadian Agency for Drugs and Technologies in Health (CADTH) recently recommended that patients who receive daratumumab should only be eligible to receive either carfilzomib or pomalidomide but not both, for relapsed MM. In order to assess the efficacy of these two agents in the relapsed setting, we utilized our national myeloma database. A total of 121 patients were reviewed, 49 patients received CAR- before POM-based (CAR-POM), and 73 patients received POM- before CAR-based (POM-CAR) therapy. In the groups selected, the median PFS was 4.93 months (95% CI, 2.76–7.07) and 5.36 months (95% CI, 3.75–6.94) for CAR-POM and POM-CAR, respectively. The median OS for patients treated with CAR-POM was 11.01 months (95% CI, 4.50–19.13), and for patients treated with POM-CAR the median OS was 10.98 months (95% CI, 8.98–19.17). In this real-world observational study, we demonstrated that both CAR- and POM-based therapies, irrespective of the order in which they were used, were effective treatment options for patients with advanced relapsed MM.

Abstract: Introduction: Bortezomib-containing regimens (BCRs) have been the standard frontline approach for the treatment of transplant ineligible multiple myeloma (TIMM) patients in Canada for many years. Based on recent randomized clinical trial results lenalidomide and dexamethasone (Ld) has become another provincially funded option in Canada in the same therapeutic space. We aimed to compare the effect of BCRs and Ld for the treatment of TIMM using the newly-formed Myeloma Canada Research Network Multiple Myeloma Database (MCRN-MM-DB) project. This web-based centralized platform can track and characterize real-world outcomes of patients treated at major Canadian institutions and includes both legacy data dating back to 2007 (from 4 centres) as well as ongoing prospective data collection (from 11 centres) analyzed up to 01/07/18. Patients and Methods: The primary objective was to assess the ORR, PFS and OS for TIMM patients treated with CyBorD/CyBorP, Ld, VMP or VD/VP, each given as reported previously but with dose-adjustments at the discretion of the treating physician to maintain patients on therapy. The two-sided Fisher exact test was used to test for differences between categorical variables. Survival curves were constructed according to the Kaplan-Meier method and compared using the log rank test; a p value of 〈 0.05 was considered significant. Results: 842 TIMM patients were evaluated. Clinical characteristics are shown in Table 1. Median OS and PFS for the entire cohort were 54.1 and 20.4 months, respectively. ORR and ≥VGPR better rates were 83% and 52% for the entire cohort. A ≥VGPR rate of 53%, 46%, 56% and 51% were observed for patients treated with CyBorD/P, VMP, Ld and VD/VP, respectively (p=0.3). The median PFS was longer for Ld patients (25 months) compared to CyBorD/CyBorP, VMP and Vd/VP (19.3, 20.5 and 13.7 months, respectively), (p=0.03, Fig 1a); there was no significant difference in PFS between the 2 different alkylating-agent containing regimens when combined with bortezomib + steroids (CyBorD/P vs VMP, p =0.9). Median OS was 51, 59.5, 29.4 and 66.5 months for those patients treated with CyBorD/CyBorP, VMP, VD/VP and Ld, respectively (p=0.07, Fig 1b). When the OS and PFS for CyBorD/P (typically given for a fixed duration of 9 cycles) were compared with Ld in a subset analysis, the p-values were 0.08 and 0.008, respectively. Conclusions: 1) OS was not significantly different in patients treated with either a bortezomib-containing triplet that includes an alkylator + steroid or continuous Ld. 2) The BCR triplets and Ld were more efficacious than the bortezomib + steroid doublet (VD/VP) for both OS and PFS although, the small sample size and adverse factors, such as frailty and comorbidities, may have influenced the findings. 3) The results in the real-world setting, i.e., a median PFS in the range of 1.5-2 years and median OS of 4.5-5.5 years, confirm triplet-based BCRs and Ld as current valid standards of care for frontline therapy in TIMM. 5) This study confirms the utility of a large comprehensive national database to benchmark current results for comparison with newer regimens as they are introduced into the Canadian therapeutic landscape. Disclosures Arleigh: Celgene: Honoraria; Janssen: Honoraria. Sebag:Janssen Inc.: Membership on an entity's Board of Directors or advisory committees; Amgen Canada: Membership on an entity's Board of Directors or advisory committees; Takeda Canada: Membership on an entity's Board of Directors or advisory committees; Celgene Canada: Membership on an entity's Board of Directors or advisory committees. Leblanc:Celgene Canada: Membership on an entity's Board of Directors or advisory committees; Janssen Inc.: Membership on an entity's Board of Directors or advisory committees; Amgen Canada: Membership on an entity's Board of Directors or advisory committees; Takeda Canada: Membership on an entity's Board of Directors or advisory committees. Louzada:Janssen: Honoraria; Celgene: Honoraria; amgen: Honoraria; pfizer: Honoraria. Venner:Janssen: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Amgen: Honoraria; Takeda: Honoraria.

Abstract: Autologous stem cell transplant (ASCT) remains an important option for eligible multiple myeloma (MM) patients as part of initial therapy. Using the Canadian Myeloma Research Group (CMRG) national database, we examined the details and outcomes of ASCT performed as first-line therapy in eligible Canadian MM patients between 2007 to 2021. We included 3821 patients with 72% receiving CyBorD induction and 2061 patients receiving maintenance, consisting of lenalidomide +/- steroids in 78.3%. The median PFS and OS for patients given a single ASCT were 35.4 and 126 months. Those receiving a second induction regimen had significantly inferior outcomes, although when maintenance was used, results were comparable regardless of the number of induction regimens administered (median PFS 55.3 vs 51.1 months [ p  = 0.11]; median OS 158.6 vs not yet reached [ p  = 0.13]). Consolidation patients had a longer median PFS (55.3 vs 34.4 months [ p  = 0.001]), but no significant gain in median OS ( p  = 0.065). Patients who received lenalidomide-based maintenance experienced a median PFS of 53.7 months and OS of 159 months. In the multivariable analysis, use of any type of maintenance therapy vs no maintenance was associated with a lower risk of progression (HR 0.52 (95% CI 0.47-0.57)) and death (HR 0.58 (95% CI 0.51-0.67)). This real-world study demonstrates that, overall, first-line treatment sequence in transplant-eligible patients produces a median OS of ≥10 years. It also highlights the contribution of post-ASCT maintenance, particularly lenalidomide given until progression.

Abstract: Lenalidomide in combination with dex (Len + dex) was introduced as treatment for relapsed/refractory myeloma in Canada over a decade ago; more recently, Len has been routinely available as part of first-line therapy, both in transplant-eligible patients-- as post-ASCT maintenance--and in transplant-ineligible patients as the Len + dex combination, and is typically given until disease progression. The management of patients progressing on Len regimens is evolving as newer anti-myeloma drugs become available. Many questions remain regarding the sequencing of treatments to obtain the longest periods of disease control between repeated relapses. We utilized the national Myeloma Canada Research Network (MCRN) Database to analyze therapy administered immediately after progression on a Len-based regimen in real-world practice. The MCRN Database contains disease-specific information on over 6000 patients reported from 13 academic centres in Canada. Between 2007 and 2019, 1482 patients (pts) progressed on Len-containing regimens in lines 1-3. 57% were male, 23% had light chain myeloma, 38% had high-risk FISH and 43% had undergone prior ASCT. Median values (range) for other pt characteristics included: age 64 range (31-92) yrs, creatinine 93 µmol/L (32-2700), B2M 329 nmol/L (range 1-7193), Hb 104 g/L (3-169), WBC 5.7 (0.12-107.6), platelets 211 (10-832), LDH 191 U/L (55-1908). The next regimen was based on bortezomib (BTZ) in 370, as part of a triplet in 278 (CyBorD, VMP); carfilzomib (CFZ) in 100, triplet in 62(KCD, KRD, KPD); ixazomib (IXA) in 75, triplet in 63 (IxaCD, IxaRD, IxaPomD); daratumumab (Dara) in 80, triplet in 75 (DaraCD, DaraRD, DaraPomD, DaraVD, DaraKD); pomalidomide (POM) in 195, triplet in 79 (PomCD/P, PomVD, PomKD); and continuation of Len in 212, triplet in 124 (RCD, RVD, RVCD). 346 (23%) did not receive any further therapy, including 79 (15%) after 1st line Len, 199 (26%) after 2nd line Len and 68 (33%) after 3rd line Len; other regimens were used in 6%, 18% and 11% of each group, respectively. The overall response rates (ORR)/median duration of treatment in months (mos) for each of the regimens included: BTZ 67%-5.8 mos; CFZ 70%-5.6 mos; IXA 60%-6.7 mos; Dara 86%-6.9 mos; POM 36%-4.0 mos; Len 39%-5.7 mos; and other 48%-3.3 mos. PFS by regimen is shown in Figure 1. 514 pts had progressed after Len as 1st line therapy, 766 after Len as 2nd line therapy and 202 after Len as 3rd line therapy. Median follow-up was 15 mos (1-130) after 1st progression and 55 mos (1-278) from diagnosis. The median PFS (95% CI) and OS (95% CI) after progression following Len as 1st line therapy were 14.5 mos (12.1-17.3) and 31.2 mos (25.3-39.0), as 2nd line therapy 8.6 mos (7.3-9.8) and 14.1 mos (11.6-16.5); and as 3rd line therapy 8.0 mos (6.7-9.9) and 11.0 mos (6.9-14.1), respectively. Figure 2 shows PFS by prior Len subgroup. More detailed analyses to assess outcomes for specific regimens after Len progression in different lines of therapy are in progress. In summary, this analysis provides an overview of treatment patterns following progression on Len in Canada, as well as the ORR, PFS and OS of different regimens. Results appeared better for proteasome inhibitor and Dara regimens after progression on Len, although some pts derived benefit from further Len regimens as well as POM-based ones; further exploration of specific treatment subgroups is ongoing. These data provide benchmarks for real-world outcomes that can be utilized as newer therapies, such as those based on immunotherapy, become available. Disclosures Reece: Amgen: Consultancy, Honoraria, Research Funding; Merck: Research Funding; BMS: Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Otsuka: Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. McCurdy:Janssen: Honoraria; Celgene: Honoraria. Song:Janssen: Honoraria; Celgene: Honoraria, Research Funding; Amgen: Honoraria; Takeda: Honoraria. Sebag:Takeda: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Leblanc:Janssen: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding. Louzada:Celgene: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Bayer: Honoraria; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. White:Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Stakiw:Janssen: Honoraria, Research Funding, Speakers Bureau; Roche: Research Funding; BMS: Honoraria; Novartis: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Lundbeck: Honoraria; Sanofi: Honoraria. Kotb:Karyopharm: Equity Ownership; Amgen: Honoraria; Merck: Honoraria, Research Funding; Celgene: Honoraria; Janssen: Honoraria; Takeda: Honoraria. Venner:J & J: Research Funding; Takeda: Honoraria; Sanofi: Honoraria; Celgene: Honoraria; Janssen: Honoraria; Amgen: Honoraria, Research Funding. OffLabel Disclosure: This abstract describes several combinations not specifically approved by the FDA but utilized in the real-world setting. However, all of the individual drugs in these combinations have been approved as single agents or in other combinations.

Abstract: Background: Recent studies evaluating tandem autologous transplantation for multiple myeloma (MM) show conflicting results in terms of efficacy. However subgroup analysis suggests that those with high-risk disease may benefit the most from tandem transplant. We used the CMRG database to compare single versus tandem ASCT for patients with MM with high-risk cytogenetics. Methods: The primary objective was to compare PFS in MM patients with high-risk cytogenetics (p53 deletion, t(4;14), t(14;16)) identified from the CMRG database undergoing front-line single or tandem ASCT from 01/2010 to 06/2019. Secondary objectives compared OS, ORR, and outcomes based on whether post-transplant maintenance was given. OS and PFS rates were calculated from the date of first ASCT using the Kaplan-Meier method. ORR was assessed by Chi-square using best response post ASCT. Results: There were 302 single and 125 tandem transplants, followed by maintenance therapy in 190 (63%) and 96 (77%) respectively. Translocation (4;14) was seen in 209 (49%), t(14:16) in 61 (15.6%) and delP53 in 222 (52%) with more than one abnormality in 65 patients. The most common induction regimen consisted of cyclophosphamide, bortezomib, and steroids, (83%) followed by bortezomib and dexamethasone (8%) and dexamethasone alone (4.7%). Forty-seven patients (11%) required reinduction prior to first ASCT with regimens including RVD (49%), Rd (23%) and others (D/DT/VD-PACE, CyBor-D, KRD, VD, IxaRD, 28%). Maintenance was prescribed to 286 patients with regimens including lenalidomide ± dexamethasone (65%), lenalidomide + proteasome inhibitor ± dexamethasone (22%), proteasome inhibitor ± dexamethasone (11%) and others (2%). Patient characteristics are summarised in table 1. The overall response rate was 93.9% (94.5% for single ASCT and 92% for tandem ASCT). The PFS at 3 years was 41.1% (single) and 45.7% (tandem) with median PFS 26 vs 35 months respectively (p=0.0621). Three year OS was 71.5% (single) and 83.8% (tandem), median OS 83 vs 89 months (p=0.0060). Both PFS and OS were improved with the use of maintenance therapy, regardless of single vs tandem transplant. PFS at 3 years was 52.1% for those receiving maintenance therapy compared to 21.7% for no maintenance (median 42 vs 16 months, p & lt;0.0001). Overall survival was 79.5% with maintenance vs 63.6% without (median 92 vs 60 months, p & lt;0.0001). Figures 1 shows PFS and OS for single or tandem transplant, with or without maintenance therapy. There was no difference in PFS or OS after a single or tandem transplant when maintenance was given. PFS for single or tandem ASCT with maintenance at 3 years was 53.7% and 46.3% respectively (p=0.527). Three year OS rates were 76.7% and 85.6% (p=0.0962). However, PFS was better with tandem compared to single ASCT when no maintenance was given. PFS at 3 years for single transplant with no maintenance was 19.0% (median 13 months) vs 48.9% (median 23.7 months) for tandem without maintenance (p=0.0084), while OS were not statistically different (62.4% vs 74.7%, median 60 months vs not reached, p=0.5271). Conclusions: Tandem ASCT does improve outcomes for MM with high-risk cytogenetics. However, the main benefit was seen in patients who did not receive maintenance therapy. Our data demonstrate the potent anti-myeloma effect of post-ASCT maintenance and raise the question of the optimal role of tandem ASCT in the modern treatment era. Disclosures Duggan: Novartis: Honoraria; Amgen: Consultancy; Celgene: Consultancy; Astra Zeneca: Consultancy; Jannsen: Consultancy. Reece:Janssen, Bristol-Myers Squibb, Amgen, Takeda: Consultancy, Honoraria; Janssen, Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Merck: Honoraria, Research Funding; Otsuka: Research Funding. Song:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Research Funding; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene/BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen, Celgene,Takeda: Consultancy, Honoraria; Otsuka: Honoraria. Jimenez-Zepeda:Janssen, Celgene, Amgen, Takeda: Honoraria. McCurdy:Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Sanofi: Honoraria; GSK: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Louzada:Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Mian:Takeda: Consultancy, Honoraria; Celgene: Consultancy; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Sanofi: Consultancy. Sebag:Celgene: Honoraria; Takeda: Honoraria; Amgen: Honoraria; Janssen: Honoraria, Research Funding. White:Takeda: Honoraria; Sanofi: Honoraria; Janssen: Honoraria; Celgene: Honoraria; Amgen: Honoraria; Karyopharm: Honoraria; Antengene: Honoraria; GSK: Honoraria. Stakiw:Lundbeck: Honoraria; Celgene: Honoraria; BMS: Honoraria; Roche: Research Funding; Janssen: Honoraria, Research Funding; Amgen: Honoraria; Novartis: Honoraria. Leblanc:Celgene Canada; Janssen Inc.; Amgen Canada; Takeda Canada: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding. Kotb:Takeda: Honoraria; Sanofi: Research Funding; Janssen: Honoraria; Amgen: Honoraria; Celgene: Honoraria; Karyopharm: Current equity holder in publicly-traded company; Merck: Honoraria, Research Funding. Venner:Janssen, BMS/Celgene, Sanofi, Takeda, Amgen: Honoraria; Celgene, Amgen: Research Funding.

Abstract: BACKGROUND: Phase 3 trials and a meta-analysis have demonstrated that Lenalidomide (Len) administration as maintenance improves the PFS and OS after ASCT performed as part of 1st line therapy. In addition, retrospective and registry studies have suggested efficacy when post-ASCT maintenance is administered after salvage ASCT in relapsed patients. Len maintenance has become the standard approach in many centres, including in Canada where it is routinely funded after 1st line ASCT and Len-base regimens are often used as maintenance after salvage ASCT in pts who have not progressed on this agent previously. The optimal management of patients (pts) progressing on this highly effective agent is less clear, however. We utilized the MCRN Database to investigate which regimens were utilized after pts progressed on Len-based therapy (post-Len Rx) and the outcomes observed with such regimens in the real-world Canadian setting. We included pts receiving Len-based regimens as maintenance following ASCT performed as part of 1st, 2nd or 3rd line therapy in this analysis, as ASCT pts are relatively young and generally tolerate combination regimens for relapsed myeloma well. METHODS: The MCRN Database is an ongoing national Canadian web-based repository of detailed information on over 6000 myeloma patients from 13 academic centres dating back to 2007. In this analysis, we evaluated the characteristics of pts progressing on post-ASCT Len-based maintenance following a transplant performed as part of the first 3 regimens administered. Pts were treated between 01/2007 until 04/2019; 305 pts had undergone 1 ASCT, 59 pts had 2 ASCTs. The next -line therapy administered at this time (post-Len Rx) was classified based on the novel agent utilized. Overall response rates (ORR), PFS from start of post-len Rx to next progression and OS (calculated from post-Len Rx to death) was calculated for these pts. Categorical comparisons were performed using the chi-square test and continuous ones using ANOVA. Survival rates were calculated using the Kaplan-Meier product-limit method; comparisons among regimens were made using the log-rank statistic. RESULTS: We identified 364 pts who had progressed on Len-based regimens given for maintenance, after ASCT, including 306 after 1st line ASCT, 51 after 2nd line ASCT and 7 after 3rd line ASCT. Len-based maintenance included Len alone in 318, Len + dex in 24 and other Len-combinations in 22. Median age was 59 yrs, 58% were male, 43.6% of 243 evaluable pts had high-risk FISH cytogenetics (del 17p, t[4;14], t[14;16] ). Median creatinine was 85 µmol/L (32-832), LDH 187 U/L (55-906) and B2M 295 nmol/L (1.8-3805). Post-Len Rx was based on bortezomib (BTZ) in 56 (15%), carfilzomib (CFZ) in 44 (12%), daratumumab (Dara) in 45 (12%), pomalidomide (POM) in 28 (8%), ixazomib (IXA) in 23 (6%), and other regimens in 27 (7%). Thirty-seven (10%) did not receive any post-Len therapy while 104 (28%) received further Len-based therapy with the addition of Dex alone in 73, or with an additional agent (BTZ, cyclophosphamide [Cy] and/or clarithromycin) in 31 (Table 1). The only significant difference in pt characteristics was a higher LDH value in the IXA and POM groups (p=0.0015). The median PFS of 327 patients who received treatment for progression on Len-based maintenance was 11 months (mos) (95% CI 8.1-13.9); OS was 39 mos (95% CI 31-60) from post-Len Rx. For the 92 (42%) pts with high-risk FISH, the median PFS was 7.9 mos (95%CI 5.3 -11.5) and OS 33 mos (95%CI 〉 23.7) compared with 11.9 mos (95%CI 8.1 -14.2) and 39.7 mos (95% CI 〉 23.9) respectively, for standard-risk pts. The ORR, median PFS and OS of each regimen from the time of post-Len Rx are summarized in Table 1, Fig 1. CONCLUSIONS: 1) the median PFS with post-Len Rx in pts progressing on Len-based maintenance after ASCT as part of 1st, 2nd or 3rd line treatment was almost 1 year for all treated pts, with longer benefit observed in pts treated with the newer proteasome inhibitors or Dara-based regimens; 2) since there was potentially confounding overlap among the agents in used in each treatment group studied-- and the 1st, 2nd and 3rd line transplant settings involved different time points in the disease course--further subset analyses of specific regimens/settings are ongoing; 3) nevertheless, the overall real-world results observed with newer agents approximate the outcomes reported in clinical trials in pts progressing on Len-based regimens after 1-3 prior lines of therapy. Disclosures Reece: Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Research Funding; Takeda: Consultancy, Honoraria, Research Funding; BMS: Research Funding; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; Otsuka: Research Funding; Amgen: Consultancy, Honoraria, Research Funding. McCurdy:Celgene: Honoraria; Janssen: Honoraria. Song:Celgene: Honoraria, Research Funding; Janssen: Honoraria; Amgen: Honoraria; Takeda: Honoraria. Leblanc:Janssen: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees. Sebag:Amgen: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. White:Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria. Stakiw:Janssen: Honoraria, Research Funding, Speakers Bureau; BMS: Honoraria; Amgen: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Celgene: Honoraria, Speakers Bureau; Roche: Research Funding; Lundbeck: Honoraria; Sanofi: Honoraria. Louzada:Janssen: Consultancy, Honoraria; Bayer: Honoraria; Celgene: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Kotb:Merck: Honoraria, Research Funding; Janssen: Honoraria; Amgen: Honoraria; Karyopharm: Equity Ownership; Celgene: Honoraria; Takeda: Honoraria. Venner:Sanofi: Honoraria; Janssen: Honoraria; Amgen: Honoraria, Research Funding; Takeda: Honoraria; Celgene: Honoraria; J & J: Research Funding. OffLabel Disclosure: This abstract describes several combinations not specifically approved by the FDA but utilized in the real-world setting. However, all of the individual drugs in these combinations have been approved as single agents or in other combinations.