Efgartigimod in adults with primary immune thrombocytopenia


Catherine Broome, MD, Georgetown University, Washington, DC, presented the results of ADVANCE IV (NCT04188379), a Phase III, multicenter, double-blinded, placebo-controlled, randomized clinical trial evaluating the efficacy and safety of intravenous efgartigimod (EFG) in adults with primary immune thrombocytopenia (ITP).

More EFG-treated participants met the primary endpoint of the proportion of chronic ITP patients with a sustained platelet count (PLT) response (PLT of ≥50×109/L in ≥4 of 6 visits between weeks 19 and 24 without intercurrent events; 21.8% versus 5.0%, respectively, p=0.0316). EFG also achieved all PLT-related secondary endpoints including extent of disease control, proportion of participants in the overall population with sustained PLT response, incidence of bleeding events, and a durable sustained platelet response in the overall population.

Compared to placebo, EFG showed an early PLT increase, higher sustained PLT response, and more weeks with PLT ≥50×109/L. The study also showed that 51.2% of participants on EFG achieved International working group (IWG) response criteria (consecutive visits ≥7 days apart with PLTs of ≥30×109/L and a 2-fold increase from baseline in the absence of bleeding events) versus 20% on placebo.


Mean IgG levels in EFG-treated participants decreased steadily over the first four weeks of treatment, after which the mean maximum reductions from baseline remained greater than 60% throughout the trial. Mean IgG levels were similar in the group receiving treatment every two weeks (q2w).

EFG was well tolerated with no new safety signals. Adverse events (AEs) were reported in 93.0% of participants in the EFG group and 95.6% in the placebo group. Most frequent AEs included bruising, headache, hematuria, and petechiae. Serious AEs were reported in 8.1% of participants in the EFG group and in 15.6% in the placebo group, and none were treatment-related. No deaths or increased risk of infection were observed.1

Talquetamab in R/R multiple myeloma: MonumenTAL-1 Phase I/II l


ASH 2022 saw results from the MonumenTAL-1 Phase I/II trial (NCT03399799/NCT04634552) of talquetamab, a first-in-class, off-the-shelf, T-cell redirecting bispecific antibody targeting GPRC5D and CD3 receptors, in heavily pre-treated patients with R/R multiple myeloma, which were presented by Ajai Chari, MD, Mount Sinai School of Medicine, New York City, NY.

In 143 pts treated at 0.4 mg/kg weekly (QW), median age was 67 years (range 46–86), with a median of five prior lines of therapy (LOT; range 2–13). Many of the patients were triple-class exposed/refractory or penta-drug exposed/refractory.


In these patients, the overall response rate (ORR) was 73% (≥VGPR: 58%; ≥CR: 29%). Responses were durable and deepened over time. Median time to response was 1.2 months (range 0.2–5.0), median time to complete response (CR) was 2.1 months (range 1.1–12.4) and median DOR was 9.3 months (95% CI, 6.6–20.2; range 1–23+). Median progression-free survival (PFS) was 7.5 months (95% CI, 5.7–9.2 [38% censored]). ORRs in pts who were triple-class refractory (72% [76/106]) and penta-drug refractory (71% [30/42]) were comparable to the overall population.

Dr Chari also presented the efficacy of dosing 0.8 mg/kg every other week (Q2W) at the meeting.

Investigators report that talquetamab demonstrated robust efficacy and manageable safety in patients with heavily pre-treated R/R multiple myeloma. The most common AEs at 0.4 mg/kg QW and 0.8 mg/kg Q2W were cytokine release syndrome (CRS; 79%/72%; grade 3: 2%/1%; grade 4: 0%/0%), dysgeusia (48%/46%; grade 3/4: not applicable [NA]), and anemia (45%/39%; grade 3: 31%/25%; grade 4: 0%/0%]). At 0.4 mg/kg QW or 0.8 mg/kg Q2W, infections occurred in 57%/50% of pts (grade ≥3: 19%/13%); 4.9%/6.2% discontinued, 8.4%/13.8% had dose delays, and 14.7%/6.2% had dose reductions due to AEs. There were two deaths due to COVID-19 (one patient at each dose).2


Gene therapy equity in sickle cell disease


Once approved in the United States, gene therapy could enable patients with sickle cell disease (SCD) patients to achieve lifelong disease remission without the concomitant risks of allogeneic transplantation. Yet, despite this promise, gene therapy has previously been projected to be cost-ineffective. At ASH, George Goshua, MD, MSc, Yale University School of Medicine, New Haven, CT, presented the first distributional cost-effectiveness analysis (DCEA), which quantifies the tradeoffs between traditional cost-effectiveness outcomes and health equity for gene therapy in SCD.

The analysis used a Markov simulation model of patients with a diagnosis of mild, moderate, or severe SCD to examine the cost-effectiveness of gene therapy versus patients treated with standard-of-care (SOC). It suggests that gene therapy can be an equitable therapeutic strategy for US patients with SCD, despite a projected minimum cost of $2.1 million once approved.

The DCEA accounted for health disparities in SCD, and based on an ability to reduce these, favors gene therapy over SOC. The traditional method of cost-effectiveness analysis, incremental cost-effectiveness ratio (ICER), has a cost-effectiveness threshold of $100,000/quality-adjusted life year (QALY). The ICER for SCD gene therapy is $144,000/QALY and therefore suggests gene therapy is not good value for money.



The investigators noted that equitable gene therapy use would include expanding eligibility to include patients with mild and moderate disease severity, in addition to those with severe SCD, assuming similar therapeutic efficacy of gene therapy across disease severity. A limitation of the study is that base-case gene therapy was assumed to be 100% effective in achieving disease remission.3

Long-term beti-cel outcomes in transfusion-dependent patients with β-thalassemia


In a combined presentation, Franco Locatelli, MD, University of California San Francisco Benioff Children’s Hospital, Oakland, CA, discussed the long-term follow-up and long-term patient-reported outcomes of patients with transfusion-dependent β-thalassemia (TDT) treated with betibeglogene autotemcel (beti-cel) gene therapy.

As of August 2021, 63 patients had received beti-cel and were followed for a median of 41.4 (9.0–87.5) months across four parent studies (two completed Phase I/II NCT01745120 and NCT02151526; two ongoing Phase III NCT02906202 and NCT03207009) and long-term follow up study LTF-303 (NCT02633943).

Transfusion independence (TI) was the primary outcome and defined as weighted average hemoglobin (Hb) ≥ 9 g/dL without packed red blood cell transfusions for ≥ 12 months. The one-time gene therapy was found to be followed by durable TI across ages and genotypes with up to seven years follow-up. Moreover, all patients who achieved TI (N=49) continue to remain TI as of last follow-up. A trend towards more patients achieving TI was observed in Phase III (34/38; 89.5%) versus Phase I/II (15/22; 68.2%).

An exploratory multivariate analysis was also carried out in patients enrolled in the Phase III trials to identify predictors of clinical outcomes. It identified that the percentage of drug product cells transduced with the BB305 lentiviral vector (LVV; %LVV+ cells) was the best predictor of clinical outcomes. DP vector copy number (VCN) and %LVV+ cells are current release assays for beti-cel.


The safety of the beti-cel treatment regimen largely reflected the known side effects of hematopoietic stem cell collection and the busulfan conditioning regimen. Overall, 18% (11/63) of patients experienced ≥1 AE considered related or possibly related to beti-cel; the most common drug product-related AEs were abdominal pain (5/63 [8%]) and thrombocytopenia (3/63 [5%]), but none were observed beyond two years post-infusion, supporting a favorable long-term safety profile. Veno-occlusive liver disease was reported in 11% (7/63) of patients and resolved after appropriate treatment. No malignancies, insertional oncogenesis, vector-derived replication competent lentivirus, or clonal predominance was observed.

In terms of long-term patient-reported outcomes, at three years post-treatment, quality of life had improved from baseline in all measures. Among patients under 18 years who achieved TI, the mean (standard error (SE)) Pediatric Quality of Life Inventory (PedsQL) score increased from 77.4 (3.4) at baseline (n=19) to 92.1 (4.2) at month 36 (n=4) (population norm = 80.9). Among adult patients with Short Form-36 Health Survey Physical Component Summary and Mental Component Summary (SF-36 PCS and MCS, respectively) data who achieved TI, the mean SF-36 PCS and MCS scores increased from 53.8 (1.4) and 50.9 (1.7) at baseline (n=12), respectively, to 55.7 (1.7) and 56.3 (1.4) at month 36 (n=9; US general population norm = 50). There were also improvements in EuroQol (EQ-5D-3L) composite index and visual analog scale (VAS) scores.

In addition, the month 36 testimonial questionnaire revealed a trend towards a positive impact on employment, school attendance, physical activity, and other aspects of life. For instance, the ability to seek employment or be employed, increased from 68.8% (11/16) of patients at baseline to 93.8% (15/16) at month 36. School absences reduced from 83.3% (15/18) missing school at baseline to 44.4% (4/9) missing school at three years.

Altogether, 100% (19/19) of patients reported an overall benefit from undergoing treatment with beti-cel, which led the investigators to suggest the treatment induces a durable quality of life improvement through year three.4,5



Written by Hannah Balfour
Edited by Thomas Southgate & Elitsa Kamberska

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