Abstract: Treating relapsed and refractory multiple myeloma has been challenging, due to a lack head-to-head trial comparisons of the various available regimens and poor cross-Canada access to currently approved regimens. New therapeutic combinations in this setting open up more options to consider, and also the possibility of greater efficacy and more judicious use of available drug classes to avoid resistance. Oncologists shared insights on how they choose between these therapeutic regimens for various patient subgroups.

Abstract: To understand the impact of therapy sequencing on progression‐free (PFS) and overall survival (OS) for the treatment of multiple myeloma (MM). The use of daily, low‐dose, lenalidomide maintenance (LM) has raised concern for fostering resistance, preventing its use in the relapsed setting. Methods We conducted a retrospective analysis of survival outcomes from the Canadian Myeloma Research Group Database. Patients were grouped based on receipt of LM after autologous stem cell transplant and receipt of lenalidomide in second‐line therapy, 575 patients were included. Results Patients treated with LM had statistically similar 2nd PFS when re‐exposed to lenalidomide in second‐line therapy compared to those receiving non‐lenalidomide‐containing regimens (10.2 vs 14.0 months, P  =.53). This cohort also had the longest 2nd OS, 18 months longer than patients treated with LM who did not receive lenalidomide at relapse (55.3 vs 37 months, P  =.004). Patients treated with LM also demonstrated deeper responses to second‐line therapy than their non‐LM counterparts. Conclusion Our data suggest that patients progressing on LM who receive lenalidomide‐containing therapy at first relapse have comparable 2nd PFS and better 2nd OS compared to non‐lenalidomide‐containing second‐line regimens. Identification of patients mostly likely to benefit from further lenalidomide‐containing therapy is paramount.

Abstract: Lenalidomide is an important component of initial therapy in newly diagnosed multiple myeloma, either as maintenance therapy post‐autologous stem cell transplantation (ASCT) or as first‐line therapy with dexamethasone for patients’ ineligible for ASCT (non‐ASCT). This retrospective study investigated treatment patterns and outcomes for ASCT‐eligible and ‐ineligible patients who relapsed after lenalidomide as part of first‐line therapy, based on data from the Canadian Myeloma Research Group Database for patients treated between January 2007 and April 2019. Among 256 patients who progressed on lenalidomide maintenance therapy, 28.5% received further immunomodulatory derivative‐based (IMiD‐based) therapy (lenalidomide/pomalidomide) without a proteasome inhibitor (PI) (bortezomib/carfilzomib/ixazomib), 26.2% received PI‐based therapy without an IMiD, 19.5% received both an IMiD plus PI, 13.5% received daratumumab‐based regimens, and 12.1% underwent salvage ASCT. Median progression‐free survival (PFS) was longest for daratumumab‐based therapy (22.7 months) and salvage ASCT (23.4 months) and ranged from 6.6 to 7.3 months for the other treatments ( P   〈  .0001). Median overall survival (OS) was also longest for daratumumab and salvage ASCT. A total of 87 non‐ASCT patients received subsequent therapy, with 66.7% receiving bortezomib‐based therapy and 13.8% receiving other PI‐based therapy. Median PFS was 15.4 and 24.8 months for bortezomib‐based and other PI‐based therapy, respectively ( P  = .404). During most of the study period, daratumumab was not funded; in this setting, switching to a different therapeutic class following relapse on lenalidomide produced the longest remissions for non‐ASCT patients. Further prospective studies are warranted to determine optimum treatment following relapse on lenalidomide, especially in the light of increased access to daratumumab.

Abstract: Introduction: Studies have demonstrated that multiple myeloma (MM) is a clinically, genetically complex and heterogeneous disease. Cytogenetic alterations identify high-risk patients in MM and are associated with a poor prognosis. They include at least one of the following at diagnosis: t(4;14), t(14;16), t(14;20), del(17p), 1q amp and 1q amp + del(1p). Autologous stem cell transplantation (ASCT) and the development of novel agents have considerably increased the median survival of MM patients. Patients with high-risk cytogenetics are associated with worse survival, and studies have shown improvement in progression-free survival with tandem ASCT when compared to single ASCT. Methods: This is a retrospective single-center study evaluating MM patients with high-risk cytogenetics at our center who have undergone a tandem autologous transplant from January 1, 2017, to December 31, 2020. Primary objective was overall response rates (ORR) and relapse rates. Secondary objectives looked at progression-free survival (PFS), overall survival (OS) using the Kaplan-Meier method. Results: From January 1, 2017, to December 31, 2020, 25 high-risk patients underwent tandem ASCT. Key patient characteristics are shown in table 1. Translocation (4:14) was seen in 8/25 (32%) patients; t(14:16) in 5/25 (20%) patients; del17p in 7/25 (28%), 1q amp in 8/25 (32%) patients, del1p + 1q amp in 5/25 (20%) patients. In terms of double hit and triple hit disease, 9/25 (36%) patients had two high risk changes and 3/25 (12%) with had three high risk changes. ISS staging wise, 5/25 (20%) patients were ISS stage I, 5/25 (20%) patients ISS stage 2 and 9/25 (36%) patients were ISS stage 3. The most common induction regimen consisted of cyclophosphamide, bortezomib, and dexamethasone (CyBorD). One patient each transitioned to daratumumab, lenalidomide and dexamethasone and PAD/CVD due to poor response. Maintenance therapy was given to 21/25 (84%) tandem ASCT patients with 5 (20%) patients receiving lenalidomide, 4 (16%) patients receiving proteasome inhibitor and 12 (48%) patients received dual maintenance. In terms of response, we recorded CR (complete response) vs VGPR (very good partial response) vs PR (partial response) after induction, 2-3 months after ASCT #1, 2-3 months after ASCT #2, 12 months after ASCT #2, and 12 months after maintenance. Following induction, 16 patients had achieved VGPR, and 9 of patients had achieved PR. After ASCT #1, 5 (55.5%) PR patients deepened their response to a VGPR. 1-3 months post ASCT #2, 3 (33.3%) PR patients deepened to a VGPR, and 2 (12.5%) VGPR patients achieved CR. 12 months after ASCT #2, 2 of the previous VGPR patients (12.5%) achieved CR, and 1 PR (11.1%) patient achieved VGPR. At the median follow-up time of 60 months, 44% of patients had relapsed. 1 patient relapsed within 1-3 months post ASCT#1. Nine other patients relapsed post ASCT #2 and maintenance except one patient who relapsed at time of ASCT #2. Univariable analysis identified hemoglobin as a statistically significant association with risk of progression or death. All patients who received any maintenance after tandem transplant were progression-free at 60 months (p & lt;0.001). Conclusion: In our retrospective study, results suggest that tandem ASCT allows for deepening of responses. Together with maintenance therapy, this contributes to the durability of further PFS prolongation in high-risk MM patients. Figure 1 Figure 1. Disclosures Lam: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Servier: Honoraria, Membership on an entity's Board of Directors or advisory committees; Hoffmann-La Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Meyers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Beigene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; SeaGen: 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; Millennium: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Johnson & Johnson: Honoraria, Membership on an entity's Board of Directors or advisory committees. Phua: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; NovoNordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria; Amgen: Honoraria. Louzada: Amgen: Honoraria; Pfizer: Honoraria; Celgene: Honoraria; Janssen: Honoraria.

Abstract: Introduction: The treatment of multiple myeloma (MM) has dramatically improved due to the availability of immunotherapies such as daratumumab (Dara). However, in Canada, myeloma treatments now account for up to 20% of some provincial drug budgets. As Dara may be effective for a prolonged period and is quickly moving into first-line therapy, the Canadian body which provides guidelines to the provincial ministries of health recommended in 2019 against open sequencing of drugs in relapsed MM. Specifically, patients who receive Dara are now only eligible for public funding for either carfilzomib (CAR) or pomalidomide (POM)--but not both-- for relapsed MM. Given the known heterogeneity of myeloma, data gaps regarding the optimal sequencing of the available agents and uncertainly regarding the impact of this new restriction on patient outcomes, we utilized our Canadian national myeloma database to assess the sequencing of these two agents. The goal of our study was to understand the efficacy of these two commonly used treatments in the relapsed setting: 1) POM- after CAR-based therapy and 2) CAR- after POM-based therapy. Methods: We performed a retrospective observational study using the Canadian Myeloma Research Group Database (CMRG-DB), analyzed up to 30/06/2020. The CMRG-DB (formerly Myeloma Canada Research Network Database/MCRN-DB) is a prospectively maintained disease-specific database with over 7000 patients enrolled from 14 academic sites across Canada and includes legacy data collected from 2007. All patients with MM who were treated for relapsed disease with approved regimens using POM after CAR, or CAR after POM were included. Our primary outcomes were overall response rates (ORR) in each respective cohort. Secondary outcomes were progression-free survival (PFS), overall survival (OS), and a landmark OS analysis from treatment initiation with the first of the two agents. Survival was estimated using Kaplan-Meier methods and compared between groups using log rank test. Results: A total of 121 patients were included: 49 treated with POM after CAR, and 72 with CAR after POM. In the POM after CAR group, the median line of treatment was 4th for POM and 3rd for CAR. In the CAR after POM group, the median line of treatment was 4th for POM and 5th for CAR. In 79/121 patients (65%), the two therapies were directly sequential, 40/49 (82%) for the POM after CAR group, and 38/72 (54%) in the CAR after POM group. Baseline characteristics and treatment details are shown in Table 1. The ORR was 51% for patients treated with POM after CAR, and 49% for patients treated with CAR after POM. The median PFS for POM after CAR was 4.93 months (95% CI, 2.76-7.07), and for CAR after POM was 5.36 months (95% CI, 3.75-6.94). The median OS for patients treated POM after CAR was 11.01 months (95% CI, 4.50-19.13), and for patients treated with CAR after POM the median OS was 10.98 months (95% CI, 8.98-19.17) (Figure 1). In a landmark analysis using the time of the treatment initiation with the first of the two agents, the median OS of patients treated with CAR after POM was 37.61 months (95% CI 26.66-46.52) and 25.32 months (95% CI 14.56-41.19) for patients treated with POM after CAR (p=0.1270) (Figure 2). Conclusion: In this real-world observational study we demonstrated that both CAR- and POM-based therapies were effective treatment options for patients with advanced relapsed MM as each produced responses in approximately 50% of patients with a median PFS of about 5 months and median OS of 11 months. These results are comparable to those noted in prospective clinical trials leading to the approval of these agents in this setting. Further, a landmark analysis showed that using both agents sequentially late in the disease course provided reasonable OS outcomes, regardless of the order in which they are sequenced. Finally, as the cost of MM therapy increases, the use of real-world data can help determine the impact of funding decisions on the outcome of patients treated in a publicly funded universal health care system such the one in Canada. Disclosures McCurdy: GSK: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Sanofi: Honoraria; Amgen: Consultancy, Honoraria. Venner:Janssen, BMS/Celgene, Sanofi, Takeda, Amgen: Honoraria; Celgene, Amgen: Research Funding. Louzada:Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. LeBlanc:Celgene: Research Funding; Celgene Canada; Janssen Inc.; Amgen Canada; Takeda Canada: Membership on an entity's Board of Directors or advisory committees. Sebag:Takeda: Honoraria; Celgene: Honoraria; Janssen: Honoraria, Research Funding; Amgen: Honoraria. Song:Celgene: Research Funding; Celgene, Janssen, Amgen, Takeda: Honoraria. Jimenez-Zepeda:Janssen, Celgene, Amgen, Takeda: Honoraria. Kotb:Takeda: Honoraria; Merck: Honoraria, Research Funding; Celgene: Honoraria; Janssen: Honoraria; Sanofi: Research Funding; Karyopharm: Current equity holder in publicly-traded company; Amgen: Honoraria. Mian:Sanofi: Consultancy; Takeda: Consultancy, Honoraria; Celgene: Consultancy; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. White:Amgen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Stakiw:Roche: Research Funding; Lundbeck: Honoraria; BMS: Honoraria; Novartis: Honoraria; Amgen: Honoraria; Celgene: Honoraria; Janssen: Honoraria, Research Funding. 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.

Abstract: Background Hospitalization is a significant risk factor for venous thromboembolism (VTE) with 25% of all VTE occurring in this setting. In patients with cancer this risk may be higher due to the inherent procoagulant state malignancy-induced, -cancer therapy and its complications. Current oncology guidelines suggest that hospitalized medical patients receive venous thromboprophylaxis with unfractionated heparin or low molecular weight heparin if their hospital stay is longer than 3 days. We sought to evaluate if patients with cancer hospitalized for management of an acute medical illness are at higher risk for failing standard anticoagulation prophylaxis with dalteparin compared to historical data. Methods This is a single-centre retrospective cohort study (London, Canada). We included adult patients; with any type of active cancer admitted for at least 3 days for treatment of an acute medical reason, who received prophylaxis with dalteparin during hospital stay. Acute medical illness was: failure to thrive; fever; need for cancer treatment as an inpatient; pain control; acute respiratory illness. The main study outcome was failure of VTE prophylaxis defined as symptomatic and objectively diagnosed pulmonary embolism (PE) or deep venous thrombosis (DVT) within 3 months of the most recent hospital discharge. Results Between January 2011 and December 2013 our hospital registered 4262 admissions of patients with cancer for treatment of an acute medical illness. 875 patients (1132 admissions) fulfilled our eligibility criteria. 681 (78%) patients were classified as having a single admission. Of those, 247 had previous but excluded admissions ("pseudo-single"), which leaves 434 patients with true single admissions. In total, there were 434 (49.5%) were males, mean age was 64.3 (SD= 13.5). Primary tumor sites were hematological (n=180); genitourinary (n= 170); lung (n=158); gastrointestinal (n=128) and others (n= 289).559 (70%) patients had stage III or IV. Reasons for admission were failure to thrive (n= 232; 26.6%); fever (n= 202; 23.3%); need for cancer treatment as inpatient (n= 154; 17.7%); pain (n=126; 14.5%); respiratory distress(n= 108; 11.6%) or pain (n= 53; 6.3%). Mean hospitalization days was 14.7 (±12). VTE occurred in 78 of 875 (8.9%) patients or 78 of 1132 admission (6.9%): 36(46%) DVT, 34 (43.5%) PE and 7 PE + DVT (8.9%). 34 of 78 (43.6%) VTE occurred within the first 14 days of admission. However, the overall risk for VTE appeared to be much more significant if the patient remained hospitalized for more than 14 days [RR=3.7 (95%CI= 1.99 - 4.71; p 〈 0.001)]. 150 (15%) patients with single admissions had a concomitant diagnosis of cancer and VTE (within 30 days of admission). A univariate analysis suggested that having had multiple admissions (OR=0.3; 95%CI=0.17- 0.54; p=0.008); being man (OR= 1.69; 95%CI: 1.03 - 2.78; p=0.039); being admitted due to respiratory distress (OR=2.6; 95%CI: 0.9 - 6.8; p=0.052) or failure to thrive (2.52; 95%CI: 1.06 - 5.9; p=0.036) were potentially significant predictors of VTE risk. However, the logistic regression confirmed that the only significant risk factor is the number of admissions (Table). When we compared our results with the pooled data from the MEDENOX, PREVENT and ARTEMIS trials we found that the incidence of VTE in the cancer patients included in the trials was the same as ours [13 of 143 patients (8.8%)] and the incidence of VTE in those without cancer was 95 of 2139 (4.5%), significantly lower compared to the cancer cohort (p=0.0004). Conclusion Our study suggests that hospitalized patients with active cancer are at high risk for VTE prophylaxis failure (8.9%) and our results are in keeping with the literature. It appears that the most important risk factor for thromboprophylaxis failure is having a first admission as a cancer patient. New VTE prophylactic strategies for this population should be investigated in future prospective studies. Table 1. Logistic Regression of potential predictors of VTE risk in hospitalized cancer patients Variable Odds Ratio 95% CI p -value Male 1.05 0.64 - 1.74 0.8270 "Pseudo-single" admission* 0.53 0.28 - 0.97 0.9182 Multiple admission* 0.29 0.16 - 0.53 0.0029 Respiratory distress 1.19 0.53 - 2.68 0.7597 Pain 1.27 0.59 - 2.71 0.5079 Failure to thrive 1.02 0.46 - 2.24 0.6820 *Reference: single admission Disclosures Louzada: janssen: Consultancy, Other: advisory board and expert opinion; pfizer: Consultancy, Other: advisory board and expert opinion; Celegene: Consultancy, Other: advisory board and expert opinion. Kovacs:Pfizer: Honoraria, Research Funding; Bayer: Honoraria, Research Funding; LEO Pharma: Honoraria; Daiichi Sankyo Pharma: Research Funding.

Abstract: Background Last year, we presented at the 56th ASH meeting (abstract 4245) preliminary results of the EXTEND study. We would like to present the complete results of this retrospective cohort study conducted in London, Canada. Current thrombosis and oncology guidelines recommend low molecular weight heparin (LMWH) for a minimum of 6 months for treatment of cancer-associated thrombosis (CAT). After the first 6 months, if malignancy is still active or anti-cancer therapy is ongoing, guidelines recommend continuation of anticoagulation, even though no guidance with respect to what best treatment option is indicated. This paucity of data led our group to evaluate what has been the preferred clinical approach for anticoagulation continuation or cessation for patients with CAT beyond the first 6 months of anticoagulation. Methods We retrospectively collected data from adult clinical patients with CAT who received anticoagulation treatment with LMWH or warfarin for at least 6 months (from January 2007 to December 2013). Inclusion criteria: 18 years old or older; any type of active cancer; any cancer stage or treatment; use of LMWH or warfarin during the first 6 months of anticoagulation for an acute CAT. Follow up period started at 6 months of anticoagulation and finished at 12 months (total of 6 months of study follow-up), or ended at time of a recurrent VTE; or death; or last follow up in clinic. Exclusion Criteria: anticoagulation for less than 6 months of; or recurrent VTE within the first 6 months of anticoagulation; or bone marrow transplantation. The primary outcome measure is VTE recurrence rate and its correlation with anticoagulation strategy after the first 6 months of anticoagulation. Results Of 417 potential patients, 289 fulfilled our inclusion criteria. 284 (98%) received LMWH and 4 (2%) warfarin during the first 6 months of treatment. There were 146 males (50.5%), median age was 66 (24 - 73). Hematological cancers were 52 (18%), and solid tumors were 143 (50.5%): the most common being lung (41/14%) and colon (55/ 19%). One hundred eighty six (64%) patients had stage III or IV malignancy. At CAT diagnosis, there were 144 DVTs, 116 PEs and 22 had both. There were 45 (32.6%) incidental PEs. At 6 months of anticoagulant therapy, 73 (25%) patients discontinued therapy and the remaining 216 patients were as follows: 139 (48%) continued on full dose LMWH, 18 (6.2%) on prophylactic LMWH, 66 (22.8%) were switched to warfarin, 3 (1%) to rivaroxaban (Table). Between 6 and 12 months of follow up, 77 patients were considered to be in remission of their cancer but 51 (66.2%) still continued on anticoagulation. In total, 18 of 289 (6.2%) patients had a recurrent VTE. Only 2 had discontinued anticoagulation. There was no significant difference in the relative risk of recurrence in patients with ongoing active malignancy or considered to be in remission [0.79 (95%CI 0.316 - 1.99); p = 0.625]. Of the 45 patients with incidental PE at first CAT, 4 (10%) presented with a recurrent VTE during our follow up period. All patients were on full dose LMWH. The only potential independent predictor for VTE recurrence was having a hematological or lung cancer [OR= 3.62 (95% CI (1.356 - 9.67) p=0.0102].Details of the univariate analysis in the table. The multivariate analysis included tumor site, discontinuation of anticoagulation or full LMWH but only tumor site was statistically significant. Conclusion Patients with CAT appear to have an ongoing high risk for recurrent VTE even though this risk appears to be lower than in the first 6 months of anticoagulants which historically ranges around 9 and 17%. In our study we were not able to accurately identify potential predictors of recurrence. However, we were able to demonstrate that patients with incidental PE are indeed at a significant recurrence risk and as such, should receive standard anticoagulation treatment. In addition, it appears that patients with hematological or lung cancer are at higher risk of recurrence. Table 1. Univariate analysis VTE recurrence risk during the 6 to 12 months after CAT diagnosis Predictor OR (95% CI) p-value Lung or Heme cancer 3.6 (1.35 - 9.67) 0.0102 Full LMWH 1.8 (0.66-4.66) 0.259 Proph LMWH 0.8 (0.11-7.00) 0.903 Oral anticoag. 0.9 (0.31-3.00) 0.949 No anticoag. 2.8 (0.64-12.65) 0.171 Stage 1.1 (0.28-3.91) 0.722 Residual VTE 1.5 (0.41-5.75) 0.507 Gender 0.8 (0.31-2.10) 0.659 Age 1.6 (0.57-4.29) 0.384 Complete remission 1.4 (0.51-3.89) 0.508 Disclosures Louzada: Celegene: Consultancy, Other: advisory board and expert opinion; pfizer: Consultancy, Other: advisory board and expert opinion; janssen: Consultancy, Other: advisory board and expert opinion. Lazo-Langner:Pfizer: Honoraria; Bayer: Honoraria.