ABSTRACT
Real-world data on the efficacy and tolerability of isatuximab with pomalidomide and dexamethasone (IsaPomDex) in relapsed/refractory myeloma patients have not been reported. In this UK-wide retrospective study, IsaPomDex outcomes were evaluated across 24 routine care cancer centers. The primary endpoint was overall response rate (ORR). Secondary endpoints included progression-free survival (PFS), duration of response (DOR) for patients who achieved an objective response (≥partial response [PR]), and adverse events (AEs). In a total cohort 107 patients, median follow up (interquartile range [IQR]) was 12.1 months (10.1-18.6 mo), median age (IQR) was 69 years (61-77). Median (IQR) Charlson Comorbidity Index (CCI) score was 3 (2-4); 43% had eGFR <60 mL/min. Median (IQR) number of prior therapies was 3 (3-3). Median (IQR) number of IsaPomDex cycles administered was 7 (3-13). ORR was 66.4%, with responses categorized as ≥ very good partial response: 31.8%, PR: 34.6%, stable disease: 15.9%, progressive disease: 15%, and unknown 2.8%. Median PFS was 10.9 months. Median DOR was 10.3 months. There was no statistical difference in median PFS by age (<65: 10.2 versus 65-74 13.2 versus ≥75: 8.5 mo, log-rank P = 0.4157), by CCI score (<4: 10.2 mo versus ≥4: 13.2, log-rank P = 0.6531), but inferior PFS was observed with renal impairment (≥60: 13.2 versus <60: 7.9 mo, log-rank P = 0.0408). Median OS was 18.8 months. After a median of 4 cycles, any grade AEs were experienced by 87.9% of patients. The most common ≥G3 AEs were neutropenia (45.8%), infections (18.7%), and thrombocytopenia (14%). Our UK-wide IsaPomDex study demonstrated encouraging efficacy outcomes in the real world, comparable to ICARIA-MM trial.
ABSTRACT
OBJECTIVES: There are no real-world data describing infection morbidity in relapsed/refractory myeloma (RRMM) patients treated with anti-CD38 isatuximab in combination with pomalidomide and dexamethasone (IsaPomDex). In this UK-wide retrospective study, we set out to evaluate infections experienced by routine care patients who received this novel therapy across 24 cancer centres during the COVID-19 pandemic. METHODS: The primary endpoint was infection morbidity (incidence, grading, hospitalization) as well as infection-related deaths. Secondary outcomes were clinical predictors of increased incidence of any grade (G2-5) and high grade (≥G3) infections. RESULTS: In a total cohort of 107 patients who received a median (IQR) of 4 cycles (2-8), 23.4% of patients experienced ≥1 any grade (G2-5) infections (total of 31 episodes) and 18.7% of patients experienced ≥1 high grade (≥G3) infections (total of 22 episodes). Median time (IQR) from start of therapy to first episode was 29 days (16-75). Six patients experienced COVID-19 infection, of whom 5 were not vaccinated and 1 was fully vaccinated. The cumulative duration of infection-related hospitalizations was 159 days. The multivariate (MVA) Poisson Regression analysis demonstrated that a higher co-morbidity burden with Charlson Co-morbidity Index (CCI) score ≥4 (incidence rate ratio (IRR) = 3, p = 0.012) and sub-optimal myeloma response less than a partial response (Subject(s)
COVID-19 Drug Treatment
, COVID-19
, Multiple Myeloma
, Aged
, Antibodies, Monoclonal, Humanized
, Antineoplastic Combined Chemotherapy Protocols/adverse effects
, COVID-19/epidemiology
, Dexamethasone
, Humans
, Multiple Myeloma/drug therapy
, Multiple Myeloma/etiology
, Neoplasm Recurrence, Local/drug therapy
, Pandemics
, Retrospective Studies
, Thalidomide/analogs & derivatives
, United Kingdom/epidemiology
Subject(s)
Antineoplastic Combined Chemotherapy Protocols/therapeutic use , COVID-19/epidemiology , Multiple Myeloma/therapy , Pandemics , SARS-CoV-2 , Antineoplastic Agents, Immunological/administration & dosage , COVID-19/prevention & control , Combined Modality Therapy , Disease Management , Forecasting , Hematopoietic Stem Cell Transplantation , Humans , Immunoglobulin Light-chain Amyloidosis/etiology , Immunoglobulin Light-chain Amyloidosis/therapy , Multiple Myeloma/complications , Multiple Myeloma/drug therapy , Multiple Myeloma/epidemiology , Palliative Care , Recurrence , Salvage Therapy , Transplantation, Autologous , Treatment Outcome , United Kingdom/epidemiologyABSTRACT
The COVID-19 pandemic has created many challenges in the management of immune thrombocytopenic purpura (ITP). The recommendation for avoidance of steroids by WHO led to the off-licence use, supported by NHS England, of thrombopoietin mimetics (TPO-RA) for newly diagnosed or relapsed ITP. This is a real-world prospective study which investigated the treatment patterns and outcomes in this setting. Twenty-four hospitals across the UK submitted 343 cases. Corticosteroids remain the mainstay of ITP treatment, but TPO-RAs were more effective. Incidental COVID-19 infection was identified in a significant number of patients (9·5%), while 14 cases were thought to be secondary to COVID-19 vaccination.
Subject(s)
COVID-19/epidemiology , Pandemics , Purpura, Thrombocytopenic, Idiopathic/therapy , Adolescent , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/adverse effects , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Aged, 80 and over , Autoimmune Diseases/complications , COVID-19/blood , COVID-19 Vaccines/adverse effects , Combined Modality Therapy , Comorbidity , Connective Tissue Diseases/complications , Contraindications, Drug , Disease Management , Female , Hemorrhage/epidemiology , Hemorrhage/etiology , Hospitals, District/statistics & numerical data , Humans , Immunoglobulins, Intravenous/therapeutic use , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Neoplasms/complications , Off-Label Use , Platelet Transfusion , Prospective Studies , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Purpura, Thrombocytopenic, Idiopathic/epidemiology , Purpura, Thrombocytopenic, Idiopathic/etiology , Tertiary Care Centers/statistics & numerical data , Thromboembolism/epidemiology , Thromboembolism/etiology , Thrombopoietin/agonists , Tranexamic Acid/therapeutic use , Treatment Outcome , United Kingdom/epidemiology , Young AdultABSTRACT
Thrombocytopenia is common in an intensive care unit (ICU) setting due to endogenous and iatrogenic factors. Despite that, thrombocytopenia in patients with severe COVID-19 infections is surprisingly uncommon. By examining the blood film of 20 ICU patients with COVID-19, we observed the presence of platelet aggregates and macrothrombocytes indicating increased platelet activity. We compared these findings with 20 blood films of non-severe COVID-19 cases where these findings were absent. These morphology features could be consistent with severe COVID-19 infection and is further evidence of the important role that platelets play when COVID-19 manifests with thrombotic complications or respiratory failure.