Outcomes of Autologous Stem Cell Transplantation in Patients with Ultra-High-Risk Multiple Myeloma.

Multiple myeloma (MM) patients with high-risk cytogenetic abnormalities have inferior survival outcomes and are underrepresented in clinical trials. There is scarce data on MM patients with more than one high-risk cytogenetic aberration (ie, ultra- high-risk MM). This study was conducted to evaluate outcomes of newly diagnosed MM patients with ultra-high-risk MM who underwent autologous hematopoietic stem cell transplantation (autoHCT). We conducted a retrospective single-center chart review analysis of adult patients with ultra-high-risk MM who underwent autoHCT between 2008 and 2018 at MD Anderson Cancer Center. High-risk cytogenetics were defined as del(17p), t(4;14), t(14;16), or 1q21 gain or amplification (1q+) by fluorescence in situ hybridization. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Seventy-nine patients with two or more high-risk cytogenetic abnormalities were included in our analysis. The median age of 61 years (range, 33.5 to 76.5 years), and 57% were female. Sixty-seven patients had two high-risk cytogenetic abnormalities, and 12 patients had three high-risk cytogenetic abnormalities. The most common combinations of high-risk abnormalities were [1q+, t(4:14)] (n = 25; 32%) and [1q+, del17p] (n = 21; 27%). The majority of patients received either bortezomib, lenalidomide, and dexamethasone (48%) or carfilzomib, lenalidomide, and dexamethasone (16%) as induction therapy. Prior to autoHCT, 52 patients (66%) achieved a very good partial response or better (≥VGPR), whereas 23 patients (29%) achieved minimal residual disease (MRD)-negative ≥VGPR. Fifty-six patients (71%) received post-transplantation maintenance therapy. Thirty-six patients (46%) achieved MRD-negative ≥VGPR at day +100 after autoHCT, and 40 patients (51%) did so at best post-transplantation response. With a median follow-up in surviving patients of 38.3 months (range, 11.9 to 104.8 months), the median PFS and OS in the entire cohort were 22.9 months and 71.5 months, respectively. For the subset of patients with three HR abnormalities, the median PFS was 15.6 months and median OS was 28.0 months. In multivariate analysis, achieving MRD-negative ≥VGPR prior to autoHCT was associated with improved PFS (hazard ratio [HR], .42; P = .045), whereas male sex (HR, .15; P = .009) and achieving MRD-negative ≥VGPR post-autoHCT (HR, .27; P = .026) were associated with improved OS. In conclusion, patients with ultra-high-risk MM have a median PFS of <24 months with the current standard of care that includes consolidation with autoHCT. These patients may benefit from earlier use of newer treatment modalities, such as chimeric antigen receptor T cell therapy and bispecific antibodies.

Single-agent lenalidomide maintenance after upfront autologous stem cell transplant for newly diagnosed multiple myeloma: The MD Anderson experience.

The optimal duration of lenalidomide (Len) maintenance for patients with multiple myeloma (MM) after autologous stem cell transplantation (autoHCT) is unknown. We conducted a retrospective single-center analysis of adult MM patients that received upfront autoHCT between 2005 and 2021, followed by single-agent Len maintenance. A total of 1167 patients were included with a median age of 61.4 (range 25.4-82.3) years, and high-risk chromosomal abnormalities in 19%. Median duration of maintenance was 22.3 (range 0.03-139.6) months. After a median follow-up of 47.9 (range 2.9-171.7) months, median PFS and OS for the entire cohort were 56.6 (95% CI 48.2-61.4) months and 111.3 (95% CI 101.7-121.5) months, respectively. In MVA, high-risk cytogenetics was associated with a worse PFS (HR 1.91) and OS (HR 1.73) (p < .001 for both). Use of KRD induction and achievement of MRD-negative ≥ VGPR before autoHCT were associated with an improved PFS (HR 0.53 and HR 0.57, respectively; p < .001 for both). Longer maintenance duration, even with a 5-year cutoff, was associated with superior PFS and OS (HR 0.17 and 0.12, respectively; p < .001 for both). A total of 106 patients (9%) developed a second primary malignancy (SPM), mostly solid tumors (39%) and myeloid malignancies (30%). Longer maintenance duration was associated with a higher risk of SPM, reaching statistical significance after >2 years (odds ratio 2.25; p < .001). In conclusion, outcomes with Len maintenance were comparable to those reported in large clinical trials. Longer duration of maintenance, even beyond 5 years, was associated with improved survival.

Impact of clonal plasma cells in autografts on outcomes in high-risk multiple myeloma patients.

Most patients with multiple myeloma (MM) undergoing autologous hematopoietic stem cell transplantation (autoHCT) eventually relapse, perhaps due to the presence of clonal plasma cells (CPC) in the autograft. We conducted a retrospective analysis to evaluate the impact of CPC in the autograft on the outcomes of high-risk chromosomal abnormalities (HRMM) patients undergoing autoHCT between 2008 and 2018. Patients were divided into CPC+ or CPC- in the autograft by next-generation flow cytometry (NGF). There were 75 CPC + autografts (18%) and 341 CPC- (82%). The CPC + group was less likely to achieve MRD-negative complete remission post-transplant (11% vs. 42%; p < 0.001). Median progression free survival (PFS) and overall survival (OS) were (12.8 vs. 32.1 months) and (36.4 vs. 81.2 months) in the CPC + and CPC- groups, respectively (both p < 0.001). Also in the subset of patients with MRD-negative ≥VGPR prior to autoHCT, those with CPC + autografts had inferior PFS (HR 4.21, p = 0.006) and OS (HR 7.04, p = 0.002) compared to CPC-. In multivariable analysis, the degree of CPC positivity in the autograft was independently predictive of worse PFS (HR 1.50, p = 0.001) and OS (HR 1.37, p = 0.001). In conclusion, both the presence and degree of CPC in the autograft were highly predictive of inferior PFS and OS.

Autologous Stem Cell Transplantation for Patients with Multiple Myeloma with Translocation (4;14): The MD Anderson Cancer Center Experience.

Translocation between chromosomes 4 and 14, t(4;14), has been reported in 15% of patients with multiple myeloma (MM) and is considered a high-risk cytogenetic abnormality associated with inferior outcomes. Autologous hematopoietic stem cell transplantation (auto-HCT) is standard of care for patients with high-risk MM, yet there are scarce data on post-transplantation outcomes of patients with t(4;14) MM. The aim of the present study was to evaluate outcomes of MM patients with t(4;14) who underwent auto-HCT and received contemporary anti-myeloma agents for induction and post-transplantation maintenance. We conducted a retrospective analysis of MM patients with t(4;14), detected by fluorescence in situ hybridization (FISH), who underwent auto-HCT between 2008 and 2018 at MD Anderson Cancer Center. Primary endpoints were progression-free survival (PFS) and overall survival (OS), and secondary endpoints were hematologic response and minimal residual disease (MRD) status after auto-HCT. MRD status in the bone marrow biopsy was evaluated using 8-color next-generation flow cytometry with a sensitivity of 1/10-5 cells. Seventy-nine patients were included (52% male), with a median age of 60 years (range, 32 to 78 years). Forty-four patients (56%) had an additional high-risk cytogenetic abnormality. Fifty patients (63%) achieved at least a very good partial response (≥VGPR) prior to auto-HCT and 20 (25%) had MRD-negative ≥VGPR. At the best post-transplantation evaluation, 90% had ≥VGPR and 63% had MRD-negative ≥VGPR. The median follow-up for survivors was 35.7 months (range, 7.7 to 111.6 months). For the entire cohort, median PFS and OS were 22.9 months and 60.4 months, respectively. Patients with MRD-negative ≥VGPR prior to transplantation had improved PFS and OS on both univariate analysis (UVA) and multivariate analysis (MVA) (hazard ratio [HR], .35 [95% confidence interval (CI), .16 to .76; P = .008] and .12 [95% CI, .03 to .44; P = .002], respectively). The presence of additional high-risk cytogenetic abnormalities was not associated with inferior PFS (P = .57) or OS (P = .70). Post-transplantation lenalidomide-based combinations were associated with improved OS in both UVA and MVA (HR, .14; 95% CI, .04 to .45; P = .001), while their impact on PFS was not statistically significant (P = .37). Our results consolidate t(4;14) as a high-risk abnormality associated with poor outcomes despite novel agent induction, auto-HCT, and post-transplantation maintenance. Despite some inherent study design limitations, including a relatively small cohort and heterogeneity in treatment, we observed that deeper pretransplantation response and post-transplantation maintenance with lenalidomide-based combination were associated with improved outcomes. Novel immune and cellular therapies are needed to improve the outcomes in patients with t(4;14).

Chimeric Antigen Receptor T-Cell (CAR T-Cell) Therapy for Primary and Secondary Central Nervous System Lymphoma: A Systematic Review of Literature.

Relapsed/refractory central nervous system (CNS) lymphoma, whether primary or secondary, is associated with poor prognosis with currently available treatment modalities, including high-dose chemotherapy-autologous stem cell transplantation. The pivotal ZUMA-1 and JULIET trials that led to FDA approval of Axicabtagene ciloleucel and Tisagenlecleucel for relapsed refractory large cell lymphoma excluded patients with CNS involvement due to concerns of increased toxicity. However, TRANSCEND study for Lisocabtagene maraleucel in relapsed refractory large cell lymphoma allowed patients with CNS involvement and reported manageable CNS toxicities in these patients. In the real-world experience, chimeric antigen receptor T-cell (CAR T) therapy has been deemed safe and effective for these patients with poor prognosis. In this systematic review, we analyzed available literature to evaluate the role of CAR T-cell therapy in both primary and secondary CNS lymphoma using Embase, Cochrane, and PubMed databases. A total of 14 studies, including 8 retrospective analyses and 6 prospective studies/clinical trials, were included in the qualitative synthesis to study the safety and efficacy of CAR T. Based on our analysis, CAR T-cell therapy appears to be associated with reasonable efficacy and a manageable safety for primary and secondary CNS lymphoma.

Leukemic stem cells and advances in hematopoietic stem cell transplantation for acute myeloid leukemia: a narrative review of clinical trials.

Objective: The purpose of this literature review is to summarize and provide a brief overview of our current understanding of acute myeloid leukemia (AML) and the role of stem cell transplantation (SCT) in its management. Background: AML is a malignant hematological disorder that is characterized by the uncontrolled proliferation of myeloid blood cells. This disease has been associated with various risk factors such as ionizing radiation, cigarette smoke, pesticides/herbicides, and chemotherapy. SCT remains the most beneficial treatment for medically fit AML patients due to superior survival outcomes. Methods: A thorough search was conducted on PubMed, Scopus, ClinicalTrials.gov, Embase and Web of Science using related keywords. Current articles on the uses of stem cell therapy in AML patients were selected. Conclusions: Long term exposure to ionizing radiation and other harmful substances such as benzene, cigarette smoke and chemotherapeutic drugs plays an important role in AML carcinogenesis. Mutations in certain genes (e.g., ASXL1, RUNX1, KIT, TP53, BCR-ABL1) seem to accelerate the process as they affect normal cellular proliferation and cell death. These events may give rise to a small subpopulation of leukemic stem cells (LSC) which continuously sustain tumor development and growth. Patients who are deemed to be medically "fit" should receive an allogenic hematopoietic stem cell transplantation (allo-HSCT) due to improved overall survival (OS) (~50%) and decreased relapsed risk (32% vs. 59%). Several studies have revealed that the medically "unfit" may benefit from more conventional agents such as azacytidine, decitabine, venetoclax or sorafenib.

Association of medical uninsurance with sociodemographic attributes in US cancer population: A cross-sectional study of NHANES data 2013 to 2018.

Medical uninsurance (MU) is associated with cancer disparities, particularly among underprivileged and minority sections of the United States. In this cross-sectional study of National Health and Nutritional Examination Survey (NHANES) data from 2013 to 2018, we evaluated sociodemographic attributes of MU disparity in the US cancer population. Those aged ≥20 years with a history of cancer and disclosed MU status were included. We calculated the descriptive statistics of the population stratified by insurance type and performed bivariate and multivariate logistic regression models to assess the association of sociodemographic attributes and MU and reported unadjusted (UOR) and adjusted odds ratios (AOR). Among the 1681 participants (US estimated, 25,982,352), 4.3% ± 0.62 were uninsured. Uninsured individuals were 13.5-year younger, largely female, less educated, and non-US born compared to insured individuals. Age (UOR: 0.94, 95% CI: 0.93-0.96), female sex (UOR: 3.53, 95% CI: 1.73-7.19), Hispanics (UOR: 4.30, 95% CI: 2.45-7.54),

Efficacy and safety of selinexor-based regimens for relapsed/refractory multiple myeloma: a systematic review of literature.

With the incorporation of novel agents in earlier lines of therapy, an increasing number of multiple myeloma patients are refractory to traditional classes of drugs. Selinexor in combination with dexamethasone has emerged as a viable option for heavily pretreated triple-class relapsed and refractory multiple myeloma (RRMM). In this systematic review, we analyzed available literature on the role of selinexor in RRMM. The Boston trial demonstrated that selinexor when combined with dexamethasone and bortezomib is associated with a better depth and duration of response without excessive toxicity, compared with bortezomib and dexamethasone alone. Similarly, selinexor in combination with carfilzomib and dexamethasone was found to have a durable response and tolerable safety profile in both carfilzomib-naive and carfilzomib refractory RRMM patients. Selinexor in combination with IMiDs (lenalidomide and pomalidomide) as well as CD38 monoclonal antibodies (daratumumab) also have promising results. Selinexor combination therapy is both safe and effective for patients with pretreated RRMM.

Durable remission of acute myeloid leukemia in an elderly patient following a limited course of azacitidine and venetoclax.

Acute myeloid leukemia (AML) is a heterogeneous hematological malignancy characterized by clonal expansion of myeloid blasts. It is the most common type of acute leukemia in adults, including elderly patients, and has historically been associated with poor outcomes in this age group. Here, we present the case of an 80-year-old woman with newly diagnosed AML with myelodysplasia-related changes. She was treated with a total of five cycles of azacitidine, two cycles as monotherapy followed by three cycles in combination with venetoclax. Therapy was stopped due to cytopenias and declining performance status. Bone marrow aspirate and biopsy immediately following treatment and again approximately four months later did not show any morphologic, immunophenotypic, or cytogenetic evidence of leukemia. The patient's clinical and performance status improved significantly with time. Follow-up labs more than three years following the completion of treatment reveal continued hematologic remission. A short treatment course of azacitidine and venetoclax with close monitoring may lead to durable responses in some patients. Further studies are necessary to determine which patients might be appropriate for treatment suspension or discontinuation while in remission.

Treatment of Light Chain Deposition Disease: A Systematic Review.

Light chain deposition disease (LCDD) is a rare hematologic disorder that can affect any organ but predominantly involves the kidneys. Existing literature is limited to case reports and small single-center retrospective series, explaining the lack of any treatment algorithms and management guidelines for patients with this disorder. In this systematic review of literature, we explored the role of standard and high-dose chemotherapy-autologous stem cell transplant for LCDD. A total of 11 studies were identified to evaluate the hematologic and renal responses to various treatment regimens. Autologous stem cell transplant and bortezomib-based regimens appear to have reasonable safety and efficacy for this rare hematologic disorder, albeit some statistical and analytical limitations. Large multicenter retrospective and prospective studies are needed to better elucidate the role of various chemotherapy regimens as well as autologous stem cell transplant for patients with LCDD.

Lenalidomide-Based Maintenance after Autologous Hematopoietic Stem Cell Transplantation for Patients with High-Risk Multiple Myeloma.

Maintenance therapy with single-agent lenalidomide (Len) after autologous hematopoietic stem cell transplantation (autoHCT) for multiple myeloma (MM) is associated with improved progression-free survival (PFS). However, MM patients with high-risk chromosomal abnormalities (HRMMs) may need a more intense regimen. We hypothesized that adding another antimyeloma drug to Len maintenance would lead to improved outcomes. We conducted this retrospective single-center chart review analysis of adult HRMM patients who underwent autoHCT between 2008 and 2018, followed by Len-based maintenance therapy. High-risk cytogenetics were defined as del(17p), t(4;14), t(14;16), 1q21 gain or amplification by fluorescence in situ hybridization. We divided patients into those who received either single-agent Len maintenance (Len-only) or Len-based combinations (Len-combo). We compared nonrelapse mortality, day 100 and best post-transplantation responses, minimal residual disease status, PFS, and overall survival (OS) between the 2 groups. We also performed sensitivity analyses using inverse probability weights to correct for potential bias owing to nonrandomization of the 2 groups. A total of 231 patients with HRMM were included in our analysis, with a median age of 62.4 years (range, 33.5 to 79.9 years), and 55% were male. There were 153 patients in the Len-only group and 78 in the Len-combo group. Len-combo regimens were either doublets (Len with dexamethasone [dex] [n = 10], elotuzumab [n = 28], or ixazomib [n = 14]) or triplets (Len with bortezomib/dex [n = 10], ixazomib/dex [n = 10], or carfilzomib/dex [n = 6]). More patients in the Len-combo group had ≥2 high-risk cytogenetic abnormalities compared with the Len-only group (32% versus 12%: P < .001). The median duration of follow-up was 40.7 months in the Len-only group and 37.0 months in the Len-combo group. For all patients, the median PFS was 25.5 months, and the median OS was 82.6 months. There was no significant between-group difference in PFS (hazard ratio [HR] 1.01; 95% confidence interval [CI], .71-1.44; P = .94) or OS (HR, .84; 95% CI, .49 to 1.43; P = .52). However, for patients with high-risk cytogenetic abnormalities other than 1q+, there was a trend toward better PFS in the Len-combo group (HR, .59; 95% CI, .32 to 1.09; P = .09), but no difference in OS (HR, .79; 95% CI, .37 to 1.65; P = .53). In this single-center retrospective analysis, the use of Len-based combinations for post-transplantation maintenance was not associated with improved outcomes in HRMM patients; however, there was a trend toward improved PFS in patients with high-risk abnormalities other than 1q+.

Outcomes after venetoclax with hypomethylating agents in myelodysplastic syndromes: a systematic review and meta-analysis.

We present a systematic review and meta-analysis to evaluate outcomes after venetoclax (VEN) with hypomethylating agents (HMA) in myelodysplastic syndromes (MDS). We performed a literature search on PubMed, Cochrane Library, EMBASE, and Clinicaltrials.gov. After screening 2004 manuscripts, 16 studies were included. Data was extracted following PRISMA guidelines. Pooled analysis was done using the meta-package by Schwarzer et al. Proportions with 95% confidence intervals (CI) were computed. We analyzed the outcomes of 373 patients from 11 retrospective studies and five phase 1 b clinical trials. Pooled complete response with or without hematological recovery was 60% (95% CI 0.49-0.7, I2= 67%, n = 373). Hematopoietic cell transplantation was performed in 32% of patients (95% CI 0.2-0.46, I2= 62%, n = 187). Overall mortality was 45% (95% CI 0.31-0.59, I2=54%, n = 140). VEN-HMA combination therapy demonstrated promising outcomes in MDS. Prospective randomized data is needed to ascertain the benefit of VEN and its impact in MDS patients.

Efficacy and safety of allogeneic hematopoietic stem cell transplant in adults with hemophagocytic lymphohistiocytosis: a systematic review of literature.

Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening disorder of the immune system. While familial HLH is usually seen in children, secondary HLH is more common in adults. Secondary HLH is associated with a wide variety of underlying conditions including infections, malignancy and autoimmune disorders. While HLH 94/04 protocol-based chemotherapy can be used for initial treatment, allogeneic hematopoietic stem cell transplant (allo-HSCT) remains the only potentially curative treatment modality for this disorder. In this systematic review, we analyzed available literature on the role of allo-HSCT in adolescent and adult patients using PubMed, Cochrane, Embase and ClinicalTrials.gov. A total of 11 retrospective studies evaluated the role of allo-HSCT for HLH. Allo-HSCT, when compared to non-HSCT approach, appears to be associated with reasonable efficacy and acceptable safety for adolescent and adult patients with HLH.

Efficacy and Safety of Daratumumab-based Regimens in Pretreated Light Chain (AL) Amyloidosis: A Systematic Review.

With recent advances in novel chemotherapeutic agents and increasing use of autologous hematopoietic stem cell transplant, there has been a significant improvement in outcomes for patients with AL Amyloidosis. Daratumumab, with its excellent safety and efficacy profile, appears to be an ideal treatment option for patients with newly diagnosed as well as relapsed refractory AL amyloidosis. In this systematic review, we analyzed the published literature on the role of Daratumumab in pretreated relapsed and refractory AL-amyloidosis patients using PubMed, Embase, Cochrane, and clinicaltrials.gov databases. A total of 16 studies evaluated the role of Daratumumab as monotherapy (DMT) or in combination with other chemotherapeutic agents (DCT). DMT and DCT were associated with promising efficacy with hematologic and organ responses (cardiac/renal) seen in 50%-90% and 50%-80% of the patients, respectively. Daratumumab appeared to be well tolerated with no significant treatment-related adverse events as DMT or DCT.

Secondary hemophagocytic lymphohistiocytosis due to nivolumab/ipilimumab in a renal cell cancer patient-A case report.

Secondary immune-related hemophagocytic lymphohistiocytosis is a rare but life-threatening complication of immune checkpoint inhibitors. HLH-2004 and HLH-1994 guidelines originally developed for primary HLH are the only available guidelines. It has proven to have a good prognosis if diagnosed promptly with discontinuation of immunotherapy and treated with corticosteroid monotherapy.

Zinc-induced hypocupremia and pancytopenia, from zinc supplementation to its toxicity, a case report.

According to one estimate, zinc supplementation is widely used in the USA by almost 37% of the elderly population above age 71. Zinc has perceived benefits of immune system enhancement without realizing the harmful effects when used in excess. One of its under-recognized side effects is hypocupremia or copper deficiency due to excessive gastrointestinal losses as excessive zinc in the gut competes with copper for absorption. If severe, hypocupremia can cause hematologic changes (anemia, leukopenia/neutropenia, thrombocytopenia, and pancytopenia) with and without neurological deficits. Since zinc-induced hypocupremia is an overlooked entity, there is a lag of 12 months between the onset of symptoms and diagnosis. Most patients usually undergo a series of costly and sometimes invasive tests such as bone marrow biopsies during this lag time. Once diagnosed, the treatment is as simple as discontinuation of zinc and oral copper supplements. Here, we present a case report of zinc-induced hypocupremia and pancytopenia in an 81-year-old lady who was taking zinc supplements for macular degeneration. The patient presented with leukopenia with neutropenia, thrombocytopenia, and moderate anemia. This case report aims to educate clinicians since this is an easily missed entity and likely more prevalent than known due to widely used zinc supplementation.

Role of Venetoclax in the Treatment of Relapsed and Refractory Multiple Myeloma.

Biomarker-driven targeted therapies have been an area of exploration for innovative therapeutic options in oncology. B-cell lymphoma-2 (BCL-2) protein is an anti-apoptotic protein expressed on the clonal plasma cells in patients with multiple myeloma (MM). MM subsets with t (11;14) have overexpression of BCL-2 and can benefit from venetoclax (VEN) when used either alone or in combination with other chemotherapeutic agents with an overall response rate (ORR) ranging from 40% to 100%. The most commonly reported grade ≥ 3 adverse effects include cytopenias and gastrointestinal side effects. This review highlights the meaningful efficacy and tolerable safety of VEN monotherapy and its combination regimens in the treatment of relapsed refractory MM.

Profile and Management of Toxicity of Selinexor and Belantamab Mafodotin for the Treatment of Triple Class Refractory Multiple Myeloma.

Treatment options are limited for multiple myeloma patients who have developed four/five drug-refractory disease. Selinexor (Sel) and belantamab mafodotin (belamaf) were recently approved by the US FDA for treatment of RRMM. The toxicity profile of these drugs is a concern since these agents are used in patients who have already undergone multiple lines of treatment. In this review, we discuss the toxicity profile and strategies for the management of toxicities of Sel and belamaf for the treatment of RRMM. We conducted a comprehensive literature search on PubMed, Embase, Cochrane, and Clinicaltrials.gov using the terms "selinexor", "belantamab", "belamaf", and "multiple myeloma" without applying any limitations based on the date of the study, language, or country of origin. The most common hematological toxicity associated with these two drugs is thrombocytopenia. Cytopenias, constitutional symptoms, gastrointestinal effects, and hyponatremia are the major toxicities of Sel. Keratopathy and anemia are the major toxicities of belamaf. Treatment modifications and dose interruption are usually needed when side effects are more than grade II. As these are newer drugs with limited data, continuous surveillance and monitoring are warranted during the treatment course with early mitigation strategies.

Ocular Toxicity of Belantamab Mafodotin, an Oncological Perspective of Management in Relapsed and Refractory Multiple Myeloma.

Belantamab mafodotin (belamaf), an antibody-drug conjugate approved for the treatment of relapsed and refractory multiple myeloma (RRMM), is an anti B-cell maturation antigen (BCMA) agent. DREAMM-1, a first in-human trial of belamaf, reported several ocular toxicities requiring dose adjustments, dose delays and treatment discontinuations. In DREAMM-1, 53% of patients in part-1 and 63% of patients in part-2 had ocular toxicity. Similarly, 73% of patients in DREAMM-2 had keratopathy (71% in 2.5 mg/kg versus 75% in 3.4 mg/kg) with the most common symptoms being blurred vision and dry eyes. Ocular toxicity of belamaf is attributed to microtubule-disrupting monomethylauristatin-F (MMAF), a cytotoxic payload of the drug that causes an off-target damage to the corneal epithelial cells. Ocular adverse events (AEs) of belamaf are more frequent at higher doses compared with lower doses. Higher belamaf dose, history of dry eyes and soluble BCMA are associated with increased risk of corneal toxicity. Absence of ocular symptoms does not exclude the possibility of belamaf-induced ocular toxicity, so patients need slit lamp and Snellen visual acuity testing to detect microcytic-like epithelial changes and visual decline. Corticosteroid eyes drops for 4-7 days prior to belamaf dose do not prevent ocular AEs and may cause steroid-related AEs instead. Keratopathy and Visual Acuity scale (KVA) is recommended to document the severity of belamaf-induced ocular toxicity and make treatment adjustments. Management of toxicity includes dosage modifications, treatment interruption or discontinuations and preservative-free artificial tears along with close ophthalmology and hematology-oncology follow-ups.