aHSCT / University of Calgary - LARVOL DELTA

Immunoglobulin Lambda Translocations Identify Poor Outcome and IMiD Resistance in Multiple Myeloma and Co-Occur with Hyperdiploidy (ASH 2018) - P=N/A; "Patients with the plasma cell malignancy multiple myeloma now benefit from treatments such as proteasome inhibitors, immunomodulatory imide drugs (IMiDs), autologous stem cell transplant, and monoclonal antibodies...b Kaplan-Meier analysis of IgL translocated [t(IgL)] patients (N=81) as compared to non-t(IgL) (N=745) for progression-free (PFS; top) and overall survival (OS; bottom). P-values were calculated using a Cox proportional hazards Wald’s test or permutation based P-value with 1,000 permutations based on the hazard ratio."

Biosimilar • Hematological Disorders • Hematological Malignancies • Immune Modulation • Inflammation • Multiple Myeloma • Oncology

Phase 3 randomized trial with daratumumab plus lenalidomide and dexamethasone (D-Rd) versus lenalidomide and dexamethasone (Rd) in patients with newly diagnosed multiple myeloma who are not suitable for transplantation (MAIA study) (DGHO 2019) - " Pts ineligible for autologous stem cell transplant were randomized 1:1 to Rd ± D. Stratification was based on ISS stage, region, and age. D-Rd in pts with transplant-ineligible NDMM significantly reduced the risk of progression or death by 45%. There are no new safety signals using D-Rd in NDMM. These data together with the phase 3 ALCYONE study support the addition of D to SoC in pts with transplant-ineligible NDMM."

Clinical • P3 data • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Neutropenia • Oncology • Respiratory Diseases • Transplantation

Phase 3 Randomized Study of Daratumumab Plus Lenalidomide and Dexamethasone (D-Rd) Versus Lenalidomide and Dexamethasone (Rd) in Patients with Newly Diagnosed Multiple Myeloma (NDMM) Ineligible for Transplant (MAIA) (ASH 2018) - "...As previously reported in 3 phase 3 studies, the addition of DARA to standards of care in both relapsed refractory (D-Rd, DARA plus bortezomib and dexamethasone [D-Vd]) or transplant-ineligible NDMM (DARA plus bortezomib, melphalan, and prednisone [D-VMP]) resulted in a ≥50% reduction in the risk of disease progression or death (Palumbo A, et al...Methods Patients ineligible for high-dose chemotherapy with autologous stem cell transplantation due to age ≥65 years or comorbidities were randomized 1:1 to Rd ± DARA...There are no new safety signals using DARA plus Rd in NDMM. These data together with the phase 3 ALCYONE study (D-VMP vs VMP) support the addition of DARA to standard of care combinations in patients with NDMM ineligible for transplant."

Clinical • Late-breaking abstract • P3 data • Biosimilar • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Neutropenia • Oncology • Transplantation

Selinexor, Pomalidomide, and Dexamethasone (SPd) in Patients with Relapsed or Refractory Multiple Myeloma (ASH 2019) - "Pomalidomide/dexamethasone achieved an ORR of 31% and progression-free survival (PFS) rate of < 4 months in patients refractory to prior bortezomib and lenalidomide...Forty patients (83%) received prior autologous stem cell transplantation (one patient received prior autologous and allogenic stem cell transplantation)... The all oral SPd combination is durable and active with an ORR of 58% in patients with disease that is lenalidomide refractory and pomalidomide naïve compared to previously published data of 31% ORR for pomalidomide/dexamethasone in a similar patient population. The median PFS on SPd of 12.2 months in pomalidomide naïve patients is longer than that observed with pomalidomide/dexamethasone (<4 months). No unexpected adverse events were noted."

Clinical • Leukopenia • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia • Transplantation

A pilot trial of autologous hematopoietic stem cell transplant in neuromyelitis optic spectrum disorder. (PubMed, Mult Scler Relat Disord) - "In our trial, AHSCT appeared safe, and moderately effective with two of three patients showing improvement in disease activity and disability. Future studies should be undertaken to determine the ideal AHSCT conditioning and the characteristics of patients likely to enter long-term remission."

Journal • Bone Marrow Transplantation • CNS Disorders • Complement-mediated Rare Disorders • Multiple Sclerosis • Neuromyelitis Optica Spectrum Disorder • Rare Diseases • Transplantation • MRI

[VIRTUAL] Efficacy of Daratumumab Containing Regimens Post Lenalidomide Maintenance in Transplant Eligible Patients: Real-World Experience from the Canadian Myeloma Research Group Database (ASH 2020) - "Introduction Lenalidomide maintenance following autologous stem cell transplant (ASCT) remains a standard of care among transplant eligible patients with newly diagnosed multiple myeloma (NDMM)...Daratumumab-containing triplet regimens have recently been introduced for these patients, typically in combination with pomalidomide (DPd), lenalidomide (DRd), or bortezomib (DVd)...The efficacy of DRd, in which daratumumab is added to an increased dose of lenalidomide, is notable and warrants further evaluation to identify which patients are most likely to benefit. Additional studies with longer follow-up are required to assess the optimal daratumumab-based regimen to be used in this growing population of patients relapsing after lenalidomide maintenance."

Clinical • Real-world evidence • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

Daratumumab, Lenalidomide, and Dexamethasone (D-Rd) Delivers a Reduction and Delay in Worsening of Pain Symptoms for Patients with Newly Diagnosed Multiple Myeloma Ineligible for Transplant (IMW 2019) - "Herein we explore the change in pain symptoms with D-Rd vs Rd treatment for patients with NDMM who were not eligible for autologous stem cell transplant (ASCT) from MAIA. Conclusion. When treated with D-Rd, patients with transplant-ineligible NDMM experienced larger reductions in pain early during therapy and a delay of time to worsening from their baseline pain level by about 14 months compared with patients treated with Rd."

Clinical • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • Pain

[VIRTUAL] Real World Characteristics and Outcomes of Patients with Relapsed and Refractory Diffuse Large B Cell Lymphoma; A Provincial Experience (ASH 2020) - "There were 10 patients (11.1%) who had had prior systemic therapy for an indolent lymphoma including 2 patients with previous autologous stem cell transplant...Patients with relapsed/refractory DLBCL have a very poor outcome and have high risk disease at relapse including advanced stage disease and poor performance status. Less than half of the patients in our study would qualify for CAR-T therapy based on clinical trial criteria. More real world data is needed to see how feasible and effective novel cellular therapy is for these high risk patients."

Clinical • Real-World Evidence • CNS Disorders • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation

[VIRTUAL] Autologous Hematopoietic Stem Cell Transplantation in Neuromyelitis Optica – Year 5 Update (MSDC 2020) - "Patients underwent non-ablative stem cell mobilization and infusion using cyclophosphamide (200mg/kg - divided as 50mg/kg/day over days -5 to -2), ATG and rituximab. The trial was closed in 2016 due to challenges in recruitment.Conclusions While the small cohort size limits interpretation, two of three patients had a marked improvement in their NMO activity and disability after AHSCT. Regimen selection and patient features may speak to the success and failures in this trial and other published studies, but it appears that AHSCT in NMO/NMOSD is a viable option worthy of further study and refinement."

CNS Disorders • Complement-mediated Rare Disorders • Neuromyelitis Optica Spectrum Disorder • Rare Diseases • Transplantation

[VIRTUAL] AL AMYLOIDOSIS SCREENING USING ABDOMINAL FAT PAD BIOPSY AND NT-PROBNP LEVELS IN MGUS PATIENTS: A RETROSPECTIVE REVIEW OF LOCAL EXPERIENCE (EHA 2020) - "Patients with advanced disease are often ineligible for autologous stem cell transplantation, and 6-month mortality rate is 24%...A centralized and dedicated MGUS clinic may be useful in diagnosing patients with such rare conditions. Other studies are investigating the role of 18F-florbetapir PET/CT (Ehman et al., 2019), MASS-FIX detection of glycosylated LC (Kourelis et al., 2018), and lambda LC variable region gene testing as screening tools for AL amyloidosis (Zhou et al., 2019)."

Retrospective data • Amyloidosis • Cardiovascular • Congestive Heart Failure • Diabetic Neuropathy • Diffuse Large B Cell Lymphoma • Gene Therapies • Heart Failure • Lymphoma • Monoclonal Gammopathy • Nephrology • Oncology • Pain • Renal Disease • Transplantation

Daratumumab Plus Lenalidomide and Dexamethasone (D-Rd) Versus Lenalidomide and Dexamethasone (Rd) in Patients with Newly Diagnosed Multiple Myeloma (NDMM) Ineligible for Transplant: Updated Analysis of Maia (ASH 2019) - " Patients with NDMM ineligible for high-dose chemotherapy and autologous stem cell transplantation due to age ≥65 years or comorbidities were randomly assigned (1:1) to receive Rd ± DARA. After longer follow up, the addition of DARA to Rd continues to demonstrate a significant PFS benefit and improved rates of deeper and more durable responses vs Rd alone in patients with transplant-ineligible NDMM. The longer follow-up also demonstrated a significant improvement in PFS2 favoring D-Rd, and no new safety concerns were observed. These results continue to support the use of D-Rd in the first line of treatment for transplant-ineligible patients with NDMM."

Clinical • CD38

Cost Effectiveness of Novel Agents in the Treatment of Multiple Myeloma: A Systematic Review (ASH 2019) - "Fifteen studies were identified involving novel agents (bortezomib, carfilzomib, thalidomide, lenalidomide, pomalidomide, ixazomib and daratumumab). Three studies assessed the cost effectiveness of novel agents in the frontline setting, 1 assessed the cost effectiveness of maintenance following autologous stem cell transplantation, and the remaining 9 assessed novel agents in the relapsed setting... This review highlights the need for ongoing research into cost effectiveness of novel agents in multiple myeloma. In general, novel agents are considered cost effective, however; there were a relatively small number of papers ion this topic and conclusions should be drawn with caution regarding the cost effectiveness of specific agents and regimens. Additionally, the studies in this review were quite heterogeneous in terms of the country of analysis, economic model, and study population, which will also influence their generalizability."

HEOR • Review

MULTIPLE MYELOMA TREATMENT LANDSCAPE FROM 2011 TO 2017 IN ALBERTA, CANADA: RESULTS FROM THE POPULATION-BASED “IDENTIFYING OUTCOMES IN REAL-WORLD MULTIPLE MYELOMA” (INFORMM) STUDY (EHA 2019) - "...The INFORMM study, an ongoing, province-wide study in Alberta, Canada (population of 4.3 million in 2018), is examining treatment patterns in a real-world setting using population-based administrative data to better understand management of newly diagnosed multiple myeloma (NDMM) and outcomes in this era of novel therapies.Aims Our goal was to analyze baseline characteristics and pre-existing comorbidities, treatment patterns (including autologous stem cell transplantation [ASCT] and lines of therapy [LOT]), and treatment attrition rates in patients with NDMM, with or without ASCT.Methods The NDMM population was derived using patient-level data sources (Discharge Abstract Database, National Ambulatory Care Reporting System, and Practitioner Claims databases), and verified by clinical input from hematologists...Treatment regimens were determined based on treatment availability during the study period, and classified as lenalidomide (LEN)-based, bortezomib (BOR)-based,..."

Clinical • Real-World Evidence