Research findings that could establish new standards of care for haematological diseases were presented at the European Haematology Association (EHA) congress in Stockholm, Sweden, over the weekend.
At the conference’s plenary session, researchers presented work demonstrating practice-changing advances for relapsed/refractory multiple myeloma, acute lymphoblastic leukaemia (ALL) and sickle cell disease.
Talquetamab a new second-line standard of care for RRMM
The first trial presented at EHA suggested that talquetamab should be considered the new second-line standard of care for relapsed/refractory multiple myeloma (RRMM).
The combinations of talquetamab plus daratumumab (Tal-D) and Tal-D with pomalidomide (Tal-DP) both significantly improved progression-free survival (PFS) and overall survival (OS), compared to daratumumab plus pomalidomide and dexamethasone (DPd).
“Tal-D with or without Pom represents a new standard of care for RRMM as early as 2L across all practice settings,” wrote the authors, led by Dr Peter Voorhees of Wake Forest University School of Medicine, Charlotte, NC, USA, in the conference abstract.
In the Phase 3 study, RRMM patients who had undergone at least one prior line of therapy (median two) were randomised to receive Tal-DP (n=287), Tal-D (n=287) or DPd (n=290).
After a median of 25 months follow-up, PFS was significantly longer in patients treated with Tal-DP and Tal-D compared to DPd (HRs 0.28 and 0.33, respectively), with 24-month PFS rates also superior (81% and 78% vs 51%) and the benefit consistent across clinically relevant subgroups.
Overall response rates were also significantly higher with Tal-DP and Tal-D compared to DPd (88% and 86% vs 78%), as were complete response (CR) or above rates (71% and 69% vs 35%) and MRD-negative ≥CR rates (52% and 46% vs 16%).
Impressively, OS was also significantly improved in patients treated with Tal-DP or Tal-D, compared to DPd (HRs 0.47 and 0.51, respectively).
Rates of grade 3-4 and 5 AEs were generally similar for Tal-DP (97% and 2%), Tal-D (79% and 4%) and DPd (96% and 5%), as were AEs leading to discontinuation (11%, 8% and 7%, respectively).
Infections of any grade, grade 3-4 and 5 were also comparable for Tal-DP (87%, 37%, 0.7%), Tal-D (84%, 28%, 2%) and DPd (83%, 41%, 2%).
While efficacy was numerically better with Tal-DP compared to Tal-D, grade 3-4 cytopenias were more frequent with pomalidomide (82% vs 52%).
Tafasitamab a new first-line option for aggressive B-cell lymphomas
Another Phase 3 trial at the same session showed that adding tafasitamab, a CD19-targeted monoclonal antibody, and lenalidomide to R-CHOP (Tafa-Len-R-CHOP) improved progression-free survival (PFS) in high-risk, aggressive B-cell lymphomas.
Patients treated with Tafa-Len-R-CHOP had a 25% lower risk of progression or death compared to R-CHOP alone, with similar improvements seen across molecular subtypes.
“Tafa-Len-R-CHOP represents a potential new 1L standard of care for patients with high-risk DLBCL or HGBL, regardless of cell-of-origin molecular subtype,” wrote the researchers, led by Professor Georg Lenz of the University Hospital in Münster, Germany, in the conference abstract.
In the study, patients with previously untreated, high-intermediate or high-risk diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma (HGBL) were randomised to receive Tafa-Len-R-CHOP (n=448) or R-CHOP (n=451).
At a median follow-up of 35 months, PFS in the general population was longer with Tafa-Len-R-CHOP than R-CHOP (HR 0.75, p=0.019) and 24-month PFS rate was higher (71% vs 63%).
In patients with centrally confirmed lymphoma subtypes (n=773), PFS and 24-month PFS rates were similarly superior with Tafa-Len-R-CHOP (HR 0.68, 73% vs 62%), with PFS also improved in patients with activated B-cell-like and germinal centre B-cell-like subtypes (HR 0.59 and 0.69, respectively).
Rates of any grade TEAE were similar in both treatment arms, although more grade ≥3 TEAEs occurred with Tafa-Len-R-CHOP than R-CHOP (87% vs 76%), while 5% of patients in both groups discontinued treatment.
Fatal TEAEs were more common with Tafa-Len-R-CHOP than R-CHOP (6% vs 4%) but the rate of mortality was lower with Tafa-Len-R-CHOP (19% vs 29%).
Blinatumomab halves risk of recurrence in high-risk ALL
Another study presented at the session showed that replacing further chemotherapy with blinatumomab can improve outcomes in children with high-risk B-cell ALL.
The risk of leukaemia-related events was halved in patients treated with blinatumomab after the first chemotherapy cycle, with rates of isolated CNS relapse particularly low and toxicity also improved.
“For the first time, in newly diagnosed ALL, highly toxic chemotherapy elements have successfully been replaced by blinatumomab demonstrating a safer but also superior anti-leukemia efficacy of immunotherapy in prognostically unfavorable paediatric B-ALL,” wrote the authors, led by Professor Martin Schrappe, of the University Medical Centre Schleswig-Holstein in Kiel, Germany, in the conference abstract.
In the Phase 3 study, children with high-risk ALL underwent induction, consolidation and one round of intensive chemotherapy, then were randomised to receive two 29-day cycles of blinatumomab (n=358), or the conventional two further cycles of intensive chemotherapy (n=351).
At a median follow-up of 2.9 years, event-free survival was significantly higher among patients treated with blinatumomab compared to those who received further chemotherapy (83% vs 70%, HR 0.51, p=0.002).
The cumulative incidence of relapse was also significantly lower with blinatumomab than with chemotherapy (12% vs 21%), as was the rate of isolated CNS relapse (0.3% vs 2.5%).
A significantly higher proportion of patients who were MRD-positive before randomisation reduced their MRD load on blinatumomab compared to chemotherapy (77% vs 46%).
Patients treated with blinatumomab also experienced lower rates of clinically relevant infectious adverse reactions (23% vs 69%, p<0.001) and a lower proportion were hospitalised with severe mucositis/stomatitis (0.3% vs 10%).
Just one patient given blinatumomab (0.3%) experienced a life-threatening adverse event, compared to 16 (5%) treated with further chemotherapy, although neurological adverse events were more common with blinatumomab (12% vs 3%).
Oral agent improves haemolytic anaemia in sickle cell disease
The final trial presented in the session demonstrated that the oral agent mitapivat could improve anaemia in sickle cell disease patients.
The data showed that sickle cell disease patients were more likely to achieve an increase in haemoglobin (Hb) concentration after six months to a year of treatment with mitapivat, compared to placebo.
In patients who achieved a Hb response, mitapivat also reduced sickle cell pain crises (SCPC), hospitalisations and fatigue.
“These data highlight that mitapivat, through its oral administration and novel mechanism for improving haemolytic anaemia, can be an effective, convenient, and disease-modifying treatment for patients with sickle cell disease,” wrote the authors, led by Dr Biree Andemariam of the University of Connecticut, CT, USA, in the conference abstract.
In the international Phase 3 trial, sickle cell disease patients (median 25 years, 58% female) were randomised to receive 100mg mitapivat (n=138) or placebo (n=69) twice daily.
In the mitapivat group, 41% of patients achieved a Hb response (≥1.0 g/dL increase in average Hb concentration from week 24 through week 52, compared with baseline), compared with 3% of patients given placebo.
Among patients who achieved a Hb response, the mean increase from baseline in Weeks 24–52 was 1.64 g/dL.
The annualised rate of SCPC was lower with mitapivat compared to placebo (2.62 vs 3.05, p=0.1213), but the difference did not reach statistical significance.
Serious AEs occurred in 20% and 29% of patients given mitapivat and placebo, respectively, with one event (0.7%) deemed to be related to mitapivat and none deemed placebo-related.
The rate of AEs leading to discontinuation was also low in both groups, at 4% and 3% with mitapivat and placebo, respectively.