Corneal Toxicity in Patients Treated by BELANTAMAB MAFODOTIN: How to Improve and Facilitate Patients Follow-Up Using Refractive Shift?

Purpose: Multiple myeloma (MM) is the second most common neoplastic blood disease worldwide. Belantamab mafodotin is a new antibody conjugate anti-B-cell maturation antigen effective against refractory myelomas. It induces intracorneal microcysts leading to refractive fluctuations. The aim of this study is to assess the value of monitoring refractive fluctuations based on the location of microcystic-like epithelial changes (MECs) to facilitate patient follow-up. Methods: This observational and multicentric study was conducted using data collected from several French centers contacted through secure email through a standardized data collection table. Results: The fluctuation of objective refraction in spherical equivalent confirms a significant myopic shift from peripheral to central forms. A decrease in the best-corrected visual acuity (BCVA), an increase in keratometry, and an increase in central epithelial pachymetry have also been observed when MECs migrate toward the center. Conclusion: The myopization found in our study in patients with central and paracentral MECs is consistent with current literature. Fluctuations in BCVA, keratometry, and epithelial pachymetry are also consistent. This study is the first real-world study and highlights heterogeneity in follow-up, emphasizing the need to establish multidisciplinary follow-up strategies. The analysis of refractive fluctuations appears to be a reproducible and noninvasive screening method that could facilitate patient follow-up without the need for consultation focused on corneal diseases.

Belantamab mafodotin in triple-refractory multiple myeloma patients: A retro-prospective observational study in Italy.

Belantamab mafodotin is the first-in-class antibody-drug conjugates targeting B-cell maturation antigen to have demonstrated effectiveness in triple-class refractory multiple myeloma (TCR-MM) patients. We performed a retrospective study including 78 TCR patients, with at least four prior lines of therapy (LOTs), who received belantamab mafodotin within named patient program and expanded access program in Italy between 2020 and 2022. Median age was 65 years (range 42-86 years), ECOG performance status was ≥1 in 45% of patients. Overall, a clinical benefit was obtained in 36 out of 74 evaluable patients (49%), with 43%, 28%, and 13.5% achieving at least partial response, very good partial response, and complete response, respectively. After a median follow-up of 12 months (range 6-21 months), median duration of response, progression-free survival (PFS), and overall survival (OS) were 14, 5.5, and 12 months, respectively. Age >70 years, good performance status and response were associated with longer PFS and OS. Keratopathy occurred in 58% of patients (G3 2.5%), corneal symptoms in 32% (G3 1.2%) and a reduction in visual acuity in 14%. Grade 3 thrombocytopenia occurred in 9% of patients. Only 3% of patients discontinued belantamab mafodotin because of side effects. This real-life study demonstrated significant and durable responses of belantamab in TCR-MM patients with four prior LOTs, otherwise ineligible for novel immunotherapies.

Effectiveness and safety of belantamab mafodotin in patients with relapsed or refractory multiple myeloma in real-world setting: The ALFA study.

OBJECTIVES: The aim of this noninterventional, retrospective ALFA study was to describe belantamab mafodotin effectiveness and safety in patients with relapsed/refractory multiple myeloma in a real-world setting in France. METHODS: Response rate, progression-free survival (PFS), overall survival (OS), and safety were assessed. RESULTS: Among the 184 patients initiating belantamab mafodotin treatment, the overall response rate was 32.7% (≥very good partial response [VGPR] 20.4%, partial response [PR] 12.3%). The median PFS (mPFS) was 2.4 months (95% confidence interval [CI]: 1.9, 3.3), and median OS (mOS) was 8.8 months (95% CI: 6.3, 11.6). According to best response, mPFS was 20.6 months (95% CI: 12.1, not reached [NR]) in patients with ≥VGPR and 7.1 months (95% CI: 4.6, 9.4) in patients with PR; mOS was NR in patients with ≥VGPR and 17.5 months (95% CI: 7.7, NR) in patients with PR. For both OS and PFS, no differences were found in subgroups of interest. The adverse events (AEs) reported in 159 patients (86.4%) were mostly ocular AEs. CONCLUSIONS: ALFA, the largest real-world cohort conducted so far, confirms the results of belantamab mafodotin as reported in the DREAMM-2 clinical trial. The clinical benefit is significant as long as the patient is a responder.

Safety and efficacy of belantamab mafodotin with pembrolizumab in patients with relapsed or refractory multiple myeloma.

BACKGROUND: Belantamab mafodotin (belamaf) has shown promising antimyeloma activity in relapsed or refractory multiple myeloma (RRMM) as a single agent. It was hypothesized that its multimodal activity may be enhanced by programmed cell death protein 1 pathway inhibition and activation of T cell-mediated antitumor responses. This study investigated the efficacy and safety of belamaf with pembrolizumab in patients with RRMM. METHODS: DREAMM-4 (NCT03848845) was an open-label, single-arm, phase 1/2 study divided into dose-escalation (part 1) and dose-expansion (part 2) phases. Patients were ≥18 years old with ≥3 prior lines of therapy including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 agent. Patients received belamaf (2.5 or 3.4 mg/kg, part 1; 2.5 mg/kg, part 2) and 200 mg pembrolizumab for ≤35 cycles. RESULTS: Of 41 enrolled patients, 34 (n = 6 part 1, n = 28 part 2) who received 2.5 mg/kg belamaf plus pembrolizumab were included in this final analysis. Sixteen patients (47%) achieved an overall response. Minimal residual disease negativity was achieved in three of 10 patients who had very good partial response or better. Five of eight patients who had prior anti-B-cell maturation antigen therapy achieved partial response or better, including two who had B-cell maturation antigen-refractory disease. Common grade ≥3 adverse events were keratopathy (38%) and thrombocytopenia (29%). Despite belamaf-related ocular events, quality-of-life measures remained stable over time. No new safety signals were observed. CONCLUSIONS: The results of DREAMM-4 demonstrated clinical activity and a favorable safety profile of belamaf plus pembrolizumab in patients with RRMM. This trial is registered at www. CLINICALTRIALS: gov as NCT03848845.

A novel agent for myeloma causing toxic keratopathy, belantamab mafodotin: a case report and literature review / Belantamabe-mafodotina, um novo agente para mieloma, causando ceratopatia tóxica: relato de caso e revisão da literatura

ABSTRACT A 60-year-old-male with refractory relapsed multiple myeloma presented with redness, pain, foreign body sensation, and blurred vision in both eyes that gradually increased after his third belantamab mafotodin infusion. Biomicroscopy revealed bilateral microcyst-like epithelial changes and epithelial crystal-like deposits, whereas in vivo confocal microscopy revealed intraepithelial and subepithelial hyperreflective deposits in corneal epithelium. Belantamab mafodotin therapy was discontinued for seven weeks due to corneal toxicity, which cleared progressively. We aim to demonstrate belantamab mafodotin-related corneal toxicity that may be detected using slit lamp and in vivo confocal biomicroscopy.

RESUMO Um homem de 60 anos, diagnosticado com mieloma múltiplo recidivante refratário, apresentou vermelhidão, dor, sensação de corpo estranho e visão turva em ambos os olhos, aumentando gradualmente após sua terceira infusão de belantamabe mafodotina. À biomicroscopia, foram observadas alterações epiteliais bilaterais semelhantes a microcistos e depósitos epiteliais semelhantes a cristais. A microscopia confocal in vivo revelou depósitos hiper-refletivos intraepiteliais e subepiteliais na córnea. Devido à toxicidade corneana, a terapia com belantamabe mafodotina foi interrompida por sete semanas e a toxicidade foi gradualmente resolvida. Nosso objetivo é demonstrar os achados à biomicroscopia confocal in vivo e à lâmpada de fenda da toxicidade corneana relacionada ao belantamabe mafodotina.

Plasma levels of BCMA-positive extracellular vesicles correlate to response and side effects in myeloma patients treated with belantamab-mafodotin.

In myeloma patients, high levels of soluble BCMA (sBCMA) can limit the efficacy of BCMA-directed therapies. Belantamab-mafodotin is a BCMA antibody-drug conjugate and shows good overall response rates in heavily pretreated patients but progression-free survival data are poor. As the drug induces apoptosis, we hypothesized that sBCMA includes extracellular vesicles (EV) and thus evaluated numbers of BCMA-EV before and during belantamab therapy in 10 myeloma patients. BCMA-EV were significantly higher in patients prior to Belantamab (median: 3227/µl; p = .013) than in other myeloma patients before therapy (n = 10; 1082/µl) or healthy volunteers (n = 10; 980/µl). During therapy, BCMA-EV showed a significant increase to a maximum of 8292/µl (p = .028). Maximal changes in BCMA-EV (Δmax = BCMA-EV at C1/maximal BCMA-EV) showed a strong inverse, logarithmic correlation (r = -.950; p < .001) with FLC ratio changes (Δmax = FLC ratio at C1/minimal FLC ratio) and BCMA-EV peaks often preceded FLC progression. Correlating increase of LDH and BCMA-EV levels, together with clinical symptoms, point to a mafodotin-induced eryptosis. In summary, BCMA-EV are a part of sBCMA, peak levels precede progression, and their measurement might be helpful in identifying resistance mechanisms and side effects of BCMA targeted therapies.

Patient-reported experiences during and following treatment with belantamab mafodotin for relapsed/refractory multiple myeloma in the DREAMM-2 study.

Introduction: Patients with relapsed or refractory multiple myeloma (RRMM) are likely to be living with persistent symptoms, especially bone pain and fatigue, and experiencing restrictions in their physical and social functioning, which reduce health-related quality of life. Methods: This qualitative interview study evaluated patients' perspectives about living with RRMM and their treatment with belantamab mafodotin, using interviews embedded in the Phase II DREAMM-2 trial (NCT03525678) with belantamab mafodotin. Patients consented to participate in up to 2 recorded telephone interviews (at treatment cycle 4 [C4] and at end of treatment [EOT]) comprising open-ended questions. Results: A total of 142 interviews were conducted with 111 unique patients. At C4, common symptoms included neuropathy, fatigue, and bone or joint pain. Improvements in symptom severity were reported by patients who responded to belantamab mafodotin. Symptoms associated with visual impairment, eye irritation, and eye pain reported during the trial were reported to be at- or near-resolution by the EOT interview. Regarding impacts of underlying MM, patients most commonly expressed concerns about changes in daily performance and lifestyle for both responders (67.5% of all impact expressions) and non-responders (63.2%). Overall, interview participants reported being satisfied with belantamab mafodotin treatment. Discussion: This qualitative patient interview study provides valuable insight into patients' symptomatic experience with belantamab mafodotin for their RRMM treatment and may help healthcare providers better anticipate their patients' real-world experience and needs when prescribing this novel agent in the clinic.

Semi-automation of keratopathy visual acuity grading of corneal events in belantamab mafodotin clinical trials: clinical decision support software.

Background: Belantamab mafodotin (belamaf) has demonstrated clinically meaningful antimyeloma activity in patients with heavily pretreated multiple myeloma. However, it is highly active against dividing cells, contributing to off-target adverse events, particularly ocular toxicity. Changes in best corrected visual acuity (BCVA) and corneal examination findings are routinely monitored to determine Keratopathy Visual Acuity (KVA) grade to inform belamaf dose modification. Objective: We aimed to develop a semiautomated mobile app to facilitate the grading of ocular events in clinical trials involving belamaf. Methods: The paper process was semiautomated by creating a library of finite-state automaton (FSA) models to represent all permutations of KVA grade changes from baseline BCVA readings. The transition states in the FSA models operated independently of eye measurement units (e.g., Snellen, logMAR, decimal) and provided a uniform approach to determining KVA grade changes. Together with the FSA, the complex decision tree for determining the grade change based on corneal examination findings was converted into logical statements for accurate and efficient overall KVA grade computation. First, a web-based user interface, conforming to clinical practice settings, was developed to simplify the input of key KVA grading criteria. Subsequently, a mobile app was developed that included additional guided steps to assist in clinical decision-making. Results: The app underwent a robust Good Clinical Practice validation process. Outcomes were reviewed by key stakeholders, our belamaf medical lead, and the systems integration team. The time to compute a patient's overall KVA grade using the Belamaf Eye Exam (BEE) app was reduced from a 20- to 30-min process to <1-2 min. The BEE app was well received, with most investigators surveyed selecting "satisfied" or "highly satisfied" for its accuracy and time efficiency. Conclusions: Our semiautomated approach provides for an accurate, simplified method of assessment of patients' corneal status that reduces errors and quickly delivers information critical for potential belamaf dose modifications. The app is currently available on the Apple iOS and Android platforms for use by investigators of the DREAMM clinical trials, and its use could easily be extended to the clinic to support healthcare providers who need to make informed belamaf treatment decisions.

Explosive Disease Progression After Single-Agent B-cell Maturation Antigen-Targeted Treatment in Multiple Myeloma: A Report of Three Cases in Sheikh Shakhbout Medical City.

Patients with "penta-refractory" multiple myeloma (MM) are challenging to treat given the limited treatment options available to them. Belantamab mafodotin is the first B-cell maturation antigen (BCMA)-targeting antibody-drug conjugate approved for the treatment of relapsed/refractory MM (RRMM). In this case report, we reviewed in detail three female patients who were diagnosed with MM international scoring system (ISS)-3 and were heavily pretreated, and refractory to CD38 monoclonal antibodies, two proteasome inhibitors, and two immunomodulatory agents. These patients were started on belantamab mafodotin and experienced rapid and explosive clinical, biochemical, and extramedullary disease progression within a short period of time. All three patients experienced worsening cytopenia, increased transfusion requirement, severe uncontrolled bony pain, recurrent infections, and frequent hospital admissions. Two of them passed away due to disease progression complications within a few months of starting belantamab mafodotin. Although belantamab mafodotin as a single agent was withdrawn from the market after the DREAMM-3 trial failed to achieve its primary endpoint in late RRMM, BCMA-targeted therapy may still be a promising treatment approach, and the role of belantamab mafodotin is yet to be revealed in combination therapy in early RRMM.

Safety, pharmacokinetics, and efficacy of belantamab mafodotin monotherapy in Japanese patients with relapsed or refractory multiple myeloma: DREAMM-11.

Belantamab mafodotin, a B-cell maturation antigen-targeting antibody-drug conjugate (ADC), was investigated in Japanese patients with relapsed/refractory multiple myeloma in Part 1 of the phase I DREAMM-11 study. Patients who had received ≥ 2 prior lines of therapy including a proteasome inhibitor and immunomodulatory agent were eligible. Eight patients received belantamab mafodotin monotherapy at 2.5 mg/kg (n = 4) or 3.4 mg/kg (n = 4) by intravenous infusion every 3 weeks on day 1 of each cycle until disease progression or unacceptable toxicity. Primary objectives were tolerability and safety, and secondary objectives included pharmacokinetics (PK) and efficacy. The most common Grade ≥ 3 adverse event was thrombocytopenia/platelet count decreased (2.5 mg/kg cohort, 100% [4/4]; 3.4 mg/kg cohort, 75% [3/4]), and no dose-limiting toxicities were observed. Ocular events, including keratopathy findings, were observed in most patients (2.5 mg/kg cohort, 100% [4/4]; 3.4 mg/kg cohort, 75% [3/4]) and were managed with dose modifications. All resolved within the study period. Overall response rates were 50% (2/4) in the 2.5 mg/kg cohort and 25% (1/4) in the 3.4 mg/kg cohort. Although PK profiles in Japanese patients varied, individual exposures overlapped with previous results in Western populations. Belantamab mafodotin monotherapy was generally well-tolerated and demonstrated clinical activity at both doses.

Real World Efficacy and Toxicity of Selinexor: Importance of Patient Characteristics, Dose Intensity and Post Progression Outcomes.

BACKGOUND: Selinexor is an orally available selective inhibitor of exportin-1 that has offered a new treatment option in relapsed or refractory myeloma (RRMM) either in combination with dexamethasone (Sd) or with bortezomib and dexamethasone (SVd). PATIENTS-METHODS: We evaluated the efficacy and toxicity of selinexor combinations in the real world, post progression therapies and their outcomes. The analysis included 44 patients with RRMM treated with Sd (N = 21, 48%) or SVd (N = 23, 52%). RESULTS: On intent-to-treat, response rate (ORR) among all treated patients was 29.5% (13/44, of which CR: 2, VGPR: 3, PR:8); ORR was 35% for SVd and 24% for Sd. Median PFS was 3.0 months for all; 6.9 months for responders (≥PR),2.7 months for Sd and 3.4 months for SVd treated patients. In univariate analysis, serum albumin <3.5 g/dl and LDH >ULN were associated with worse PFS (P = .001 and P = .032, respectively).The OS of the whole cohort exceeded one year while serum albumin <3.5 gr/dl and LDH>ULN were associated with worse OS. After progression to Sd/SVd, 20 patients received further therapy; on ITT, the ORR was 40% (8/20) and the subsequent PFS was 3.4 months. The most common adverse events were fatigue, thrombocytopenia and nausea, while the most recorded grade 3 or 4 side effect was thrombocytopenia; 56% (25/44) of patients required dose reduction, however, this was not associated with inferior PFS. CONCLUSION: In conclusion, selinexor-based therapy provides an additional treatment option in the real word setting and with appropriate dosing and toxicity management a subset of patients may have significant benefit.

Real-World Effectiveness and Safety of Belantamab Mafodotin Monotherapy in Triple-Class Refractory Multiple Myeloma.

B-cell maturation antigen (BCMA) is a promising therapeutic target for multiple myeloma (MM). The aim of this study was to assess the effectiveness and tolerability of monotherapy with the conjugated anti-BCMA monoclonal antibody belantamab mafodotin in triple-class refractory patients with MM in real-world practice. Patients refractory to at least one proteasome inhibitor, one immunomodulatory drug, and one anti-CD38 monoclonal antibody received belantamab mafodotin at 2.5 mg/kg intravenously every 3 weeks. Overall, 27 patients with a median age of 65 years (range 41-81) were included. Of these, 52% were male and the median number of prior lines of treatment was 5 (4-10). The overall response rate (partial response or better) was 52%, whereas the disease control rate (stable disease or better) was 70%. The median progression-free survival (PFS) was 2 months (95%CI: 0-7), whereas the median PFS among the responders was 12 months (95%CI: 6-18). Regarding the toxicity profile, the most common toxicity was eye toxicity, in 44% of the patients. Keratopathy grade 2-3 was reported in 33.3% of the patients. In conclusion, belantamab mafodotin showed a safety and efficacy profile consistent with the results of the registrational study. Importantly, heavily pretreated patients who responded to treatment derived a substantial survival benefit.

Belantamab Mafodotin: From Clinical Trials Data to Real-Life Experiences.

Despite the recent approval of novel immunotherapies, such as immunomodulatory drugs, proteasome inhibitors and anti-CD38 monoclonal antibodies, Multiple Myeloma (MM) remains incurable, and the acquisition of triple-refractoriness leads to really dismal outcomes in even earlier lines of therapy. More recently, innovative therapeutic strategies targeting B cell maturation antigen (BCMA), highly expressed on the plasma cell surface, are drawing different future landscapes in terms of effectiveness and outcomes. Belantamab Mafodotin, a first-in-class anti-BCMA antibody-drug conjugate, demonstrated good efficacy and safety profile in triple-refractory patients in the phase 2 DREAMM-2 trial, and it was approved for the treatment of MM triple-exposed patients with >4 prior lines of therapy. Here, starting from Belantamab Mafodotin clinical trials and also exploring combination studies and different schedules in order to improve its efficacy and toxicity, we focused on real-life experiences all over the world, which have confirmed clinical trial data and encourage further Belantamab Mafodotin investigations.

Belantamab Mafodotin in Patients with Relapsed/Refractory Multiple Myeloma: Results of the Compassionate Use or the Expanded Access Program in Spain.

Belantamab-mafodotin (belamaf) is a novel antibody-drug conjugate targeting B-cell maturation antigen that showed anti-myeloma activity in patients with relapsed and refractory multiple myeloma (RRMM). We performed an observational, retrospective, and multicenter study aimed to assess the efficacy and safety of single-agent belamaf in 156 Spanish patients with RRMM. The median number of prior therapy lines was 5 (range, 1-10), and 88% of patients were triple-class refractory. Median follow-up was 10.9 months (range, 1-28.6). The overall response rate was 41.8% (≥CR 13.5%, VGPR 9%, PR 17.3%, MR 2%). The median progression-free survival was 3.61 months (95% CI, 2.1-5.1) and 14.47 months (95% CI, 7.91-21.04) in patients achieving at least MR (p < 0.001). Median overall survival in the entire cohort and in patients with MR or better was 11.05 months (95% CI, 8.7-13.3) and 23.35 (NA-NA) months, respectively (p < 0.001). Corneal events (87.9%; grade ≥ 3, 33.7%) were the most commonly adverse events, while thrombocytopenia and infections occurred in 15.4% and 15% of patients, respectively. Two (1.3%) patients discontinued treatment permanently due to ocular toxicity. Belamaf showed a noticeably anti-myeloma activity in this real-life series of patients, particularly among those achieving MR or better. The safety profile was manageable and consistent with prior studies.

The Effect of Belantamab Mafodotin on Primary Myeloma-Stroma Co-Cultures: Asymmetrical Mitochondrial Transfer between Myeloma Cells and Autologous Bone Marrow Stromal Cells.

Belantamab mafodotin (belamaf) is an afucosylated monoclonal antibody conjugated to the microtubule disrupter monomethyl auristatin-F (MMAF) that targets B cell maturation antigen (BCMA) on the surface of malignant plasma cells. Belamaf can eliminate myeloma cells (MMs) through several mechanisms. On the one hand, in addition to inhibiting BCMA-receptor signaling and cell survival, intracellularly released MMAF disrupts tubulin polymerization and causes cell cycle arrest. On the other hand, belamaf induces effector cell-mediated tumor cell lysis via antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis. In our in vitro co-culture model, the consequences of the first mentioned mechanism can be investigated: belamaf binds to BCMA, reduces the proliferation and survival of MMs, and then enters the lysosomes of malignant cells, where MMAF is released. The MMAF payload causes a cell cycle arrest at the DNA damage checkpoint between the G2 and M phases, resulting in caspase-3-dependent apoptosis. Here, we show that primary MMs isolated from different patients can vary widely in terms of BCMA expression level, and inadequate expression is associated with extremely high resistance to belamaf according to our cytotoxicity assay. We also reveal that primary MMs respond to increasing concentrations of belamaf by enhancing the incorporation of mitochondria from autologous bone marrow stromal cells (BM-MSCs), and as a consequence, MMs become more resistant to belamaf in this way, which is similar to other medications we have analyzed previously in this regard, such as proteasome inhibitor carfilzomib or the BCL-2 inhibitor venetoclax. The remarkable resistance against belamaf observed in the case of certain primary myeloma cell cultures is a cause for concern and points towards the use of combination therapies to overcome the risk of antigen escape.

Use of Oral Antivirals Ritonavir-Nirmatrelvir and Molnupiravir in Patients with Multiple Myeloma Is Associated with Low Rates of Severe COVID-19: A Single-Center, Prospective Study.

In patients with multiple myeloma (MM), SARS-CoV-2 infection has been associated with a severe clinical course and high mortality rates due to the concomitant disease- and treatment-related immunosuppression. Specific antiviral treatment involves viral replication control with monoclonal antibodies and antivirals, including molnupiravir and the ritonavir-boosted nirmatrelvir. This prospective study investigated the effect of these two agents on SARS-CoV-2 infection severity and mortality in patients with MM. Patients received either ritonavir-nirmatrelvir or molnupiravir. Baseline demographic and clinical characteristics, as well as levels of neutralizing antibodies (NAbs), were compared. A total of 139 patients was treated with ritonavir-nirmatrelvir while the remaining 30 patients were treated with molnupiravir. In total, 149 patients (88.2%) had a mild infection, 15 (8.9%) had a moderate infection, and five (3%) had severe COVID-19. No differences in the severity of COVID-19-related outcomes were observed between the two antivirals. Patients with severe disease had lower neutralizing antibody levels before the COVID-19 infection compared to patients with mild disease (p = 0.04). Regarding treatment, it was observed that patients receiving belantamab mafodotin had a higher risk of severe COVID-19 (p < 0.001) in the univariate analysis. In conclusion, ritonavir-nirmatrelvir and molnupiravirmay prevent severe disease in MM patients with SARS-CoV-2 infection. This prospective study indicated the comparable effects of the two treatment options, providing an insight for further research in preventing severe COVID-19 in patients with hematologic malignancies.

Real-World Outcomes of Belantamab Mafodotin for Relapsed/Refractory Multiple Myeloma (RRMM): Preliminary Results of a Spanish Expanded Access Program (EAP).

INTRODUCTION: Belantamab mafodotin (BM) is a new anti-BCMA antibody-drug conjugate, recently approved for triple-class relapsed and refractory multiple myeloma (RRMM). We assessed real-world outcomes with BM in patients under the Spanish Expanded Access Program (EAP). METHODS: We conducted an observational, retrospective, multicenter study including RRMM patients who received ≥ 1 dose of BM (Nov 2019 to Jun 2021). The primary endpoint was overall response rate (ORR). Secondary endpoints were progression-free survival (PFS), overall survival (OS), and incidence of treatment-emergent adverse events (TEAEs). RESULTS: Thirty-three patients were included with a median of 70 years of age (range, 46-79 years). Median time from diagnosis was 71 months (range, 10-858 months). Median prior lines was 5 (range, 3-8 lines); 90% of patients were triple-/quad-/penta-refractory; 48% showed high-risk cytogenetics. Median BM doses was 3 (range 1-16 doses), with a median follow-up of 11 months (6-15 months). ORR was 42.2% (≥ VGPR, 18.2%). Median PFS was 3 months (95% CI 0.92-5.08) in the overall population, and 11 months (HR 0.26; 95% CI 0.10-0.68) for patients who achieved ≥ PR. PFS was not significantly different according to age, cytogenetic risk, and prior therapy lines. OS was 424 days (95% CI 107-740). Non-hematological TEAEs (57.6% of patients; 30.3% ≥ G3) included keratopathy (51.5%; 21.2% ≥ G3) and patient-reported vision-related symptoms (45.5%). Keratopathy was resolved in 70.6% of patients. G3 hematological TEAEs was 18.2%, thrombocytopenia (21.2%). Dose reductions due to TEAEs: 30.3%; delays: 36.4%. Treatment discontinuation causes: progression (54.5%), toxicity (non-ocular; 6%/ocular; 6% /ocular + non-ocular toxicity; 3%), death (6%), and patient's decision (3%). CONCLUSIONS: BM showed relevant anti-myeloma activity in RRMM with a manageable safety profile. These results corroborate those observed in the BM pivotal trial.

Long-lasting effect of belantamab mafodotin in heavily pretreated multiple myeloma.

Belantamab mafodotin (BLMF) is an interesting therapeutic alternative for multiple myeloma (MM) patients pretreated with immunomodulatory drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies. Scientific evidence on BLMF provides immature data about progression-free survival and overall survival by short follow-up of patients with poor prognoses. Cases with long follow-ups could provide additional information about BLMF. This case reports a patient with MM treated with BLMF who had received nine previous lines of therapy with a follow-up of 11 months. No complete response was obtained. However, no disease progression was observed and the patient was still alive at the end of this work. BLMF showed manageable adverse effects. Our patient presented advanced disease, good functional status at the beginning of BLMF treatment, and elevated levels of lactate dehydrogenase during BLMF therapy. The influence of these last two factors was not evaluated in clinical trials. This relationship should be assessed more deeply in future studies.