Introduction

Multiple myeloma (MM) is a malignancy of terminally differentiated plasma cells. The treatment of MM has evolved rapidly over the last two decades, with the advent of novel therapeutics leading to significant increases in patient survival [1, 2]. Despite substantial improvement in patient outcomes, MM remains incurable in most patients and disease relapse is expected [3]. The mainstays of treatment for newly diagnosed and relapsed patients include various combinations of proteosome inhibitors (PIs; [bortezomib, carfilzomib, ixazomib]), immunomodulatory drugs (IMiDs; [lenalidomide, pomalidomide, thalidomide]), anti-CD38 monoclonal antibodies (mAbs; [daratumuab, isatuximab]), as well autologous stem cell transplantation (ASCT) in select fit patients based on Phase 3 trials [4,5,6,7,8,9,10,11].

Ultimately, patients become triple class refractory (TCR; refractory to a PI, IMiD, and anti-CD38 mAb) or, increasingly, penta-drug refractory (refractory to bortezomib, carfilzomib, lenalidomide, pomalidomide, and daratumumab). With the upfront use of triplets and now quadruplets including a PI, IMiD, anti-CD38 mAb, and dexaemethasone in first line [12,13,14], this is occurring after first- or second-line treatment in many jurisdictions. Once patients are refractory to treatment, outcomes with current widely available therapeutics are almost universally poor, with median progression free survival (mPFS) and median overall survival (mOS) ranging from 3.9–4.4 months and 10.5–11.1 months, respectively [15, 16]. Therefore, new agents exploiting novel targets are required. B cell maturation antigen (BCMA) is a cell surface protein universally expressed on plasma cells and has become a therapeutic target for patients with MM using various platforms including BCMA targeted antibody-drug conjugates (ADCs), bispecific antibodies (bispecifics), and chimeric antigen receptor T cells (Car-Ts) [17,18,19,20,21].

Belantamab mafodotin (belamaf) is a first in class afucosylated humanized anti-BCMA IgG1 mAb conjugated to microtubule disrupting monomethyl auristatin F (MMAF). It binds to FcγRIIIa on plasma cells resulting in activation and recruitment of immune effector cells and enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) [17]. Belamaf has single agent activity as demonstrated in the DREAMM-1 First In Human trial, in which patients with heavily pre-treated relapsed/refractory MM (RRMM) enrolled in Part 2 of the study had an overall response rate (ORR) of 60% (95% confidence interval [CI]: 42.1–76.1); 46.2% (95% CI: 19.2–74.9) in patients who had previously had > five prior therapies and 68.2% (95% CI: 45.1–86.1) in those with ≤ five prior lines [22]. Notably, single agent belamaf had an ORR of 38.5% (95% CI: 13.9–68.4) in patients refractory to an IMiD, a PI and were daratumumab exposed [23]. At median follow up of 12.5 months, the mPFS was 12 months (95% CI: 3.1–not estimable), 6.2 months in those that were triple class exposed (TCE) [23]. The single agent clinical activity was subsequently confirmed in the Phase 2, DREAMM-2 trial, where all patients were TCR. For the patients that received single agent belamaf (2.5 mg/kg every three weeks) the ORR was 31% (97.5% CI: 20.8–42.6) and the median duration of response (mDOR) was 11 months [4]. Finally, the DREAMM-3 Phase 3 study compared single agent belamaf to pomalidomide and dexamethasone (Pd). Although the study did not meet its primary endpoint of PFS superiority over Pd (11.2 vs 7.0 months; HR 1.03; 95% CI: 0.72–1.47), the study reaffirmed the clinical activity of belamaf in heavily pre-treated patients.

The promising single agent activity in heavily pre-treated patients has supported the development of belamaf-combination regimens. The Canadian Myeloma Research Group ALGONQUIN trial is a two-part study evaluating belamaf in combination with Pd for patients that are lenalidomide refractory and PI exposed. We have recently reported outcomes of the dose and schedule optimization of the combination. We identified 2.5 mg/kg as the maximally tolerated dose (MTD) combined with standard dosing of Pd and a recommended part 2 dose (RP2D) and schedule of belamaf 2.5 mg/kg administered every eight weeks (Q8W) [24]. For the intent to treat population, the ORR was 87.7% and the PFS was 21.8 months. Herein, we report a post- hoc subgroup analysis of patients treated on the ALGONQUIN study who were TCE and/or TCR.

Methods

Study design and participants

The ALGONQUIN study is a multicenter, open-label, single arm, 2-Part study (ClinicalTrials.gov Identifier: NCT03715478) evaluating the combination of belamaf +Pd conducted at nine Canadian academic centres. Part 1 was a dose-exploration phase using a standard 3 + 3 dose escalation design to determine the MTD patients enrolled at belamaf doses of 1.92, 2.5, and 3.4 mg/kg combined with standard dose Pd; up to 12 patients could be enrolled in each dose cohort and the option of additional dosing cohorts to better inform the RP2D was included in the protocol. Part 2 consisted of an expansion cohort of 26 patients to further evaluate safety and efficacy of the RP2D established in Part 1 and an additional cohort of 12 patients (cohort 2b) treated at the RP2D but exploring an alternative dose modification schedule for corneal adverse events (AEs).

We enrolled patients with RRMM aged ≥18 with Eastern Cooperative Oncology Group (ECOG) performance status of 0–2 and adequate bone marrow, cardiac and renal function who had progressive disease after ≥ one treatment line including a PI and lenalidomide (combined or in separate lines). Patients were excluded if they had unstable comorbidities or laboratory abnormalities that may affect their safety, ability to provide consent, compliance with study procedures, or if they had concurrent or prior corneal epithelial disease except for mild punctate keratopathy.

Data were collected by the sponsor with all authors having full access to data interpretation, manuscript preparation, revision, and final approval.

Procedures

In the dose escalation cohort, patients received intravenous belamaf at the following doses: 1.92 mg/kg every four weeks (Q4W) (cohort 1); 2.5 mg/kg Q4W (cohort 1a), 2.5 mg/kg Q4W split 50% on days one and eight (cohort 1b), 2.5 mg/kg loading dose cycle 1 day 1 then 1.92 mg/kg Q4W thereafter (cohort 1c), 3.4 mg/kg Q4W split 50% on days one and eight (cohort 2), 2.5 mg/kg Q8W (cohort 3a), 2.5 mg/mg every 12 weeks (Q12W) (cohort 3b). Based on the Part 1 results, patients treated in the Part 2a and 2b dose expansion portion received belamaf 2.5 mg/kg Q8W. For both Part 1 and Part 2 pomalidomide was administered using the standard dose of 4 mg daily for 21 of 28 days with dexamethasone 40 mg (20 mg if >75 years) weekly. Patients were required to undergo ophthalmology assessments prior to each dose of belamaf and use preservative free lubricating eye drops. Treatment was continued until disease progression, prohibitive toxicity, intolerance, or withdrawal of consent. Protocol-defined dose modifications (omissions, delays, reductions) were made independently for each drug as clinically indicated based on the grade of the toxicity.

Assessments

In all patients, clinical assessments, laboratory tests for hematology and biochemistry and disease assessments were done on day 1 of each cycle. Clinical activity was assessed according to the International Myeloma Working Group Uniform Response Criteria for Multiple Myeloma [25]. The National Cancer Institute Common Terminology for Adverse Events (CTCAE version 5.0) were used to grade severity of AEs. Visual acuity was assessed by the Snellen method and corneal epithelial changes were graded by prespecified keratopathy and visual acuity (KVA) scale [26].

Study endpoints/outcomes

The primary endpoints of the trial were to determine the MTD and RP2D of belamaf in combination with Pd in Part 1, as well as the ORR (PR or better) in response evaluable patients treated at the RP2D in Part 1 (cohort 3a) and Part 2 (cohort 2a). Secondary endpoints included determining the PFS, OS, DOR, and safety in the intention to treat population as previously described [24]. In this post-hoc subgroup analysis, we evaluated the ORR, PFS, DOR, OS, and AEs in patients who were TCE (exposed to a PI, lenalidomide, and an anti-CD38 mAb) and/or TCR (refractory to a PI, lenalidomide, and anti-CD38 mAb) defined as disease that is non-responsive to therapy or progression during or within 60 days of drug administration.

Statistical analysis

No formal statistical power calculations were performed to determine the sample sizes for the Part 1 of the trial or for this subgroup analysis. All analyses of outcomes from Part 1 of the study were descriptive, with results reported by dose and schedule, as relevant. For the RP2D cohort a sample size of 35 was obtained to detect a response rate of 0.60 against 0.30 as the historical response rate [2, 3], a one-side binomial proportional test was performed, type I error rate was set at 0.05 and the power was set at 97%. Also, a 10% drop rate was considered. Efficacy counts (rates) were calculated for ORR in the dose escalation and all patients treated at the RP2D that had two consecutive response assessments. Data are summarized by all treated patients, dose group, and RP2D-dosed patients. Median PFS, DOR, and OS (with 95% CI) were analyzed using the Kaplan-Meier method. Number of patients at risk and event-free rates (with 95% CI) at specific months were displayed within the survival curves. SAS 9.4 (SAS Institute Inc.) was used as a statistical tool for all analyses.

Results

Patient disposition and baseline characteristics

Baseline characteristics are presented in Table 1. Between 04 January 2019 and 14 September 2022, 99 patients were enrolled and received at least one dose of belamaf. Of these, 69 patients were identified as TCE or TCR and are the focus of this analysis, of whom 41 were treated at the RP2D. Fifty-six of the 69 (81.2%) were TCR across all cohorts. The median age of this cohort was 67 years (36–85) and 47.8% (33/69) were female. Twenty three percent (16/69) of patients were International Staging System (ISS) Stage III and 22% (15/69) had high risk cytogenetics [del(17p) and/or translocation t(4:14) and/or translocation t(14,16)]. Median number of prior therapies was 3 (range 1–5). In this subgroup analysis, 100% of patients were exposed to lenalidomide, a PI, and anti-CD38 mAb (100% TCE), with 98.6% (68/69) of patients refractory to lenalidomide, 82.6% (57/69) refractory to a PI, and 100% refractory to anti-CD38, resulting in 81.2% (56/69) TCR patients.

Table 1 Baseline characteristics by Part 1, RP2D and all patients.
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At the data cutoff of 30 June 2023, 56 (57%) of 99 patients enrolled had progressed or died; 31 (45%) of 69 TCE, 14 (34%) of 41 TCE treated at the RP2D and 27 (48%) of 56 patients that were TCR and treated across all cohorts (Fig. 1).

Fig. 1: CONSORT flow diagram for TCR/TCE patients enrolled onto the Algonquin Study.
figure 1

AE adverse event, belamaf-Pd belantamab mafodotin, pomalidomide and dexamethasone, Q8W every 8 weeks, RP2D recommended Part 2 dose. *Includes 8 from the dose escalation treated with 2.5 mg/kg Q8W.

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Efficacy

The clinical efficacy data for this subgroup of patients is shown in Table 2 and by dosing cohort for Part 1 patients in Supplementary Table 1. The combination of belamaf-Pd demonstrated deep and durable responses in patients that are TCE/R. The ORR and very good partial response (VGPR) rate or better were 86.4% (57/66) and 63.6% (42/66) for the overall cohort, respectively, and 88.6% (31/35) and 62.8% (22/35) for patients treated across various dose cohorts in Part 1, respectively. Specifically, for all TCE patients, (16/66) 24.2% achieved a complete response (CR) or stringent CR (sCR), 39.4% (26/66) achieved VGPR, and 22.7% (15/66) achieved a confirmed PR. For the 57 responders, the median time to first response of PR or better was 61 days (range, 56–82) with responses being durable with a median DOR of 22·1 months (95% CI, 18.3–not yet reached [NYR]). At a median follow up of 12.2 months (range, 0.9–34.4), the median PFS for the overall TCE group was 19.6 months (95% CI, 17.8–NYR), with median OS of 34.4 months (95% CI, 22.5–NYR) (Table 2). While the estimated median time to next treatment (TTNT) was not reached, 74.2% of patients were still on belantamab treatment without next line of treatment at 24 months (Fig. 2a and Supplementary Fig. 1). For all TCE patients that achieved a CR/sCR, the median PFS was not reached with 71.4% (95% CI, 47.8–100.0%) estimated to be progression free at 2 years (Supplementary Fig. 2).

Table 2 Efficacy outcomes by part 1, RP2D, all patients, and by TCR status.
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Fig. 2: Kaplan–Meier curves for median PFS, DOR and OS by overall and RP2D.
figure 2

a PFS, DOR and OS KM curves for all TCE (n = 69) and all TCR (n = 56). b PFS, DOR and OS for RP2D patients (n = 41). CI confidence interval, Est estimated, DOR duration of response, HR hazard ratio, KM Kaplan–Meir, NE not estimable, OS overall survival, PFS progression-free survival, RP2D recommended part 2 dose, TCE triple-class exposed, TCR triple-class refractory.

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For TCR patients, refractory to all three classes of anti-myeloma drugs, 84.9% (45/53) achieved confirmed responses including 12 CR or stringent CR, 24 VGPR, and 9 PR. Median DOR was preserved at 22.5 months (95% CI, 18.1–NYR), with median PFS of 19.6 months (95% CI, 15.7–NYR) and median OS of 34.4 months (95% CI, 22.5–NYR) for patients with TCR disease.

For the 41 TCE patients treated at the RP2D the ORR was 84.6% (33/39), ≥VGPR 66.7% (26/39) with a median DOR NYR (95% CI, NYR–NYR). At a median follow up of 12.2 months (range, 1.2–28.3) the median PFS was NYR (95% CI, 18.1–NYR) while the estimate 2-year PFS, DOR and OS were 57.0% (95% CI, 41.1–79.1), 68% (95% CI, 51.0–90.7), and 77.2% (95% CI, 62.3–95.6), respectively (Fig. 2b).

Toxicity

Adverse events reported in >20% of patients in this cohort, serious adverse events (SAEs) and median belamaf dose intensity are presented in Tables 3a, b and 4 respectively, and were similar for TCE and TCR patients. Ninety one percent (63/69) and 95% (39/41) of patients experienced a least one Grade ≥3 AE in the overall cohort and at RP2D, respectively. The most common non hematologic Grade ≥3 AEs were keratopathy (48% in all patients, 46% at RP2D), decreased visual acuity (42% in all patients, 44% at the R2PD) and infection (24.6% in all patients, 19.5% at the RP2D). With respect to Grade ≥3 hematologic toxicity, thrombocytopenia was seen in 27% of the overall cohort and 27% in RP2D patients, with 36% and 34% experiencing neutropenia respectively (Table 3a). Fatal SAEs of Grade ≥3 were experienced by 3% and 2% of patients overall and at the RP2D, respectively. Median dose holds for Grade ≥3 AEs were 5 and 4, respectively (Tables 3b and 4).

Table 3 a. Adverse events experienced by >20% of patients by overall cohort and RP2D patients. b. Serious adverse events and median dose holds by overall cohort and RP2D patients.
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Table 4 Summary of belamaf dosing by Part 1, RP2D, and all patients.
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Discussion

In this subgroup analysis of belamaf-Pd treated patients on the ALGONQUIN trial, we demonstrate that TCE/TCR patients attain high response rates with durable remissions, with ORRs of 86%/85%, mPFS of 19.6/19.6 months, mDOR 22.1/22.5 months, and mOS of 34.4/34.4 months respectively. Patients treated at the RP2D had an ORR of 85% with median PFS NYR and estimated 24-month PFS rate of 57%. These findings support belamaf-Pd as a highly clinically active therapeutic option in patients who are TCE/TCR.

The majority of patients with RRMM will soon be exposed and/or refractory to PIs, IMIDs, and anti-CD38 mAbs after first- or second-line therapy given the increasing use of triplet [4,5,6] and quadruplet [12,13,14] therapies earlier in the disease course. The MAMMOTH study first reported on the outcomes of patients that are refractory to anti-CD38 mAbs of which 79.1% were TCR. The data were sobering demonstrating an ORR of 31% and mOS of 8.6 months. The results of the MAMMOTH study were validated in the prospective LocoMMotion study that evaluated the outcome of TCE patients treated with widely available, real-life standard of care (SOC) treatments [15]. For patients that were TCE/TCR the ORR was 29.8%/25.1%, mPFS 4.6/3.9 months, and mOS 12.4/11.1 months, respectively. Consistently, in a retrospective cohort study of 199 TCR patients treated with SOC regimens in Canada, the ORR was 40%, the mPFS similarly poor at 4.4 months, and mOS was 10.5 months [16]. These studies not only serve as a benchmark for comparison to new therapies being evaluated in in this setting but also highlight the urgent unmet clinical need of this expanding patient population.

The phase 2 DREAMM-2 trial enrolled RRMM patients who had received 3 or more lines of therapy and were refractory to IMiDs, PIs and an anti-CD38 mAb. For the patients that received single agent belamaf (2.5 mg/kg Q3W) the ORR was 32% (97.5% CI: 21.7–43.6) ref. [27]. Although the mPFS was 2.8 months, for those patients that achieved a PR or better, the responses were durable with a mDOR of 11.0 months (95% CI, 4.2–not reached) and a mOS that was not reached with estimated 1-year survival probability of 87% (95% CI, 69%–95%). Although these results confirmed the single agent activity of belamaf in TCR patients, they suggested a need to improve on the response rates. The results of the ALGONQUIN study demonstrate that adding Pd to belamaf the improvement of ORR to 85% translated to a more clinically meaningful mPFS of 19.6 months in TCR patients.

Certainly, an evolving option for patients who are TCE are the most novel T-cell re-directing therapeutics, chimeric antigen receptor (CAR) T-cell therapies and the bispecific Abs, many of which share a common target with belamaf. The anti-BCMA bispecific Abs, teclistamab and elranatamab, received regulatory approval based on the results of the single-arm phase 2 studies, MajesTEC-1 and MagnestisMM-3, respectively. Patients with a median of 5 prior treatment lines of whom 78% were TCR on the Majestec-1 trial had an ORR of 63% with median PFS of 11.3 months (95% CI, 8.8–17.1) ref. [28]. In a retrospective subgroup analysis, the ORR was preserved in TCR patients. Ninety-seven percent of patients enrolled in the MagnetisMM-3 study were TCR. Patients treated with elranatamab achieved an ORR of 61% and with an estimated 51% of patients remaining in remission at 15 months [29]. In addition, the CD3 redirecting bispecific Abs targeting antigens beyond BMCA are demonstrating clinical activity in RRMM. In the phase 2 MonumenTal-1 trial, patients with ≥3 prior lines including ≥1 PI, ≥1IMiD, and ≥1 anti-CD 38 mAb received Talquetamab, a G protein-coupled receptor, family C, group 5, member D (GPRC5D) bispecific [30]. In this cohort, of whom 84% were TCR, the ORR was 74% with median PFS of 7.5 and 11.9 months for the weekly and Q2W cohorts respectively [30]. Finally, in the first-in-human study of cevostamab, a CD3 T-cell engaging bispecific antibody that targets Fc receptor-homolog 5 (FcRH5), 84.5% of patients were TCR and the ORR was 56.7% in those receiving doses of 132–198 mg Q3W [31]. In context, and with the known limitations of cross-trial comparisons, our study using the anti-BCMA ADC belamaf in combination with Pd in this subgroup analysis of patients who were universally TCE and almost all TCR appears to have comparable if not improved ORR and PFS.

It is important to consider the updated results recently presented from the phase 1b/2 Cartitude-1 trial demonstrating unprecedented results in RRMM. In this study, patients with a median 6 prior lines of treatment, 88% TCR, treated with ciltacabtagene autoleucel (cilta-cel) had an ORR of 98% and mPFS of 34.9 months [32]. The initial results of the randomized Cartitude-4 trial of cilta-cel vs. SOC regimens (PVd or DPd) were also recently presented. In this trial, patients with one to three prior lines of treatment who were lenalidomide refractory also showed high response rates, with an ORR in the intent to treat population of 85% vs. 67% in the standard regimen group, with a 12-month PFS of 76% vs 49%, respectively [33]. Alternatively, results from the randomized KarMMa-3 trial of idecabtagene vicleucel (ide-cel) vs. SOC regimens in patients with two to four prior lines of treatment showed an ORR of 71% and mPFS 13.3 months in the ide-cel group [34], noting however that the percent of TCR patients in Cartitude-4 was much lower at 14.4% compared 65% in the KarMMa-3. Despite the exciting cilta-cel data, we currently face several issues limiting access to Car-T therapy in most jurisdictions, due to challenges with product access (manufacturing capacity, distribution, reimbursement), as well as patient factors such as rapid disease progression, access to effective bridging, financial toxicity, and fitness. As such, many patients and providers will need to consider alternative anti-BCMA treatments for most TCE/TCR patients in the immediate future, until Car-T is more accessible to the global RRMM population.

With access becoming more widely available to anti-BCMA approaches and with studies evaluating these agents in earlier lines of therapy, the age-old question of treatment sequencing in myeloma remains relevant. Data is emerging on the effectiveness of BCMA targeted agents in patients previously exposed to an alternate BCMA directed therapy. This evolving literature, as well as further work on mechanisms of response and resistance, will be paramount as we aim to select optimal treatments for individual patients. Recently presented data are reassuring, suggesting that prior exposure to BMCA targeted ADCs such as belamaf does not preclude responses to other BMCA targeting agents. For example, in the cohort C (n = 40) of the MajesTEC-1 study 72.5% of patients were ADC exposed and received teclistamab. The ORR for patients previously treated with a BMCA targeting ADC was 52.5% ref. [35]. Furthermore, a pooled analysis of patients with prior anti-BCMA directed therapy (n = 87) treated with elranatamab on MagnetisMM studies revealed an ORR and mDOR for patients with prior BMCA-targeting ADC of 42.4% and 13.6 months, respectively [36]. Twenty-four patients treated in cohort C of the Cartitude-1 trial (n = 20) had prior anti-BCMA treatment, with ORR of 61% for those with prior ADC (n = 13) and a mPFS of 12.3 months [37], demonstrating in principle that patients treated with anti-BCMA ADCs can respond to anti-BCMA Car-T treatment. Finally, data on sequencing of belamaf after BMCA directed therapies are more limited but in a real-world study, 19 patients received anti-BMCA Car-T (n = 12), bispecific Ab (n = 6) or treatment with belamaf. Response to belamaf was similar in those with prior BMCA exposure compared to BMCA-naïve patients with a mPFS of 4 months reported in both groups [38]. Ongoing trials of the growing BCMA arsenal and their analyses in these patient subgroups will be imperative to optimizing the use of BMCA containing regimens such as belamaf-Pd in the treatment algorithm for individual patients.

The safety profile was similar for TCE patients compared to the intent to treat population (Supplementary Table 2). This includes the risk of serious infections that has emerged as a significant challenge with T-cell re-directing therapies. Indeed, the relative low rate of Grade ≥3 infections (24.6%) is consistent with what is reported in the DREAMM3 study [39] and further supports the notion that belamaf poses less infection risk. Nevertheless, it is important to discuss that ocular toxicity remains the main clinical challenge with belamaf administration, with no additional safety signals found in this analysis. In this subgroup, Grade ≥ 3 ocular AEs were keratopathy (48% in all patients, 46% at RP2D) and decreased visual acuity (42% in all patients, 44% at the R2PD). Longer dosing intervals did not compromise efficacy in our study, similar to the findings with the use of belamaf given every 12 weeks in combination with lenalidomide and dexamethasone resulting in 11–13% Grade 3 visual acuity changes [40]. To evaluate if ocular toxicity can be further improved, we have added an additional cohort to part 2 of this trial where by patients will receive belamaf 1.92 mg/m2 every 8 weeks with standard Pd, based on emerging data from the DREAMM-9 trial that this dose resulted in reduced toxicity with preserved response rates [41]. We have also embarked on an optional ocular sub-study using bandage contact lenses to attempt to reduce corneal toxicity, with results to be reported at a later date. While optimization efforts continue, routine eye examinations remain a requirement for patients being treated with belamaf, and clinicians must be informed on symptom management and dose-modification. However, there are divergent challenges with alternative novel agents in this patient population, including infection (61.8–76%) and CRS (50.6–72%) with the anti-BCMA bispecifics [28, 29], CRS/ICANS (84–92%/17–18%) with Car-T therapy [20, 32], and dysgeusia (37–65%), skin (24–67%) and nail changes (20–57%) with talquetamab [42], supporting the need for individualized treatment based on patient and disease characteristics and patient choice.

While our results are encouraging, we recognize there are several limitations to our study, including the short follow up time and small number of patients. In addition, the results of our phase 1–2 trial need to be confirmed in a large phase 3 trial with an appropriate comparator, such as the DREAMM-8 trial which compares belamaf-Pd to PVd and is expected to read out soon [43].

In summary, patients with TCE/TCR disease treated with belamaf-Pd on the ALGONQUIN trial experienced clinical benefits that are markedly superior to those reported with real-life SOC therapies and competitive with other BCMA agents including the bispecifics and ide-cel. These data support the use of belamaf-Pd as a highly effective therapy to address the unmet need of particularly challenging RRMM patient population.