Summary of TCT 2020 highlights – part 1: Conditioning regimens for AML and MDS

This article is based on an overview of the International Academy for Clinical Hematology webinar delivered by Bipin Savani on April 1, 2020. It is a first part of a series summarizing the highlights from the Transplantation & Cellular Therapy (TCT) 2020 meeting.

Abstract 6: Myeloablative fractionated busulfan conditioning regimen in older patients: Results of phase II study¹

The authors assessed whether toxicity, non-relapse mortality and graft-versus-host disease (GvHD) associated with an intense conditioning regimen using busulfan and allogeneic hematopoietic stem cell transplantation (allo-HSCT) and could be reduced by giving the same dose of busulfan over a longer period.

Treatment schedule

• Starting on Day -20, and followed by another dosing on Day -13 and Days -6 to -3, patients received busulfan at 80 mg/m² to achieve an area under the curve dose of 20 000 μmol/min (equivalent of 12.8 mg/kg). Intravenous fludarabine 40 mg/m² was added on day -6 for 3 days.

GvHD prophylaxis

• Cyclophosphamide (50 mg/kg) on Day 3 and 4
• Tacrolimus +/- mycophenolate mofetil starting on Day 5

Patient characteristics

• In total, 78 patients with hematological malignancies, including 24% with acute myeloid leukemia (AML), 27% with myelodysplastic syndromes (MDS), and 40% with myeloproliferative disease (MPD) were enrolled on the study
• Median age was 61 (39–70) years
• Majority of patients (77%) had low or intermediate disease risk score
• Most patients had the hematopoietic cell transplantation-specific comorbidity index (HCT-CI) score of 1–2 or ≥3 (44% and 42% of patients, respectively)
• Peripheral blood was the predominant source of cells (94%)
• Engraftment was successful in all patients

Safety

• GvHD
  • Acute GvHD at 100 days
    • Grade 2–4 in 35% (95% CI, 24–43%)
    • Grade ≥3 in 5% (95% CI, 0–10%) of patients
  • Chronic GvHD at one year
    • All Grades in 9% (95% CI, 2–16%) of patients
• Most frequent Grade III-V treatment-emergent adverse events
  • Infections (55%)
  • Neutropenic fever (41%)
  • Mucositis (15%)
  • Elevated bilirubin (12%)

Efficacy

• Overall survival (OS) at 1 year was 85% (95% CI, 76–94)
• Progression-free survival at 1 year was 81% (95% CI, 73–91)
• Non-relapse mortality (NRM) at 1 year was 8% (95% CI, 2–14)
• Relapse rate at 1 year was 11% (95% CI, 4–19)
• Outcomes by disease risk index
  • OS in low/intermediate group was significantly higher than in the high/very high group (95%; 95% CI, 90–100 vs 46%; 95% CI, 26–83; p <0.0001)
  • Patients in the high/very high risk group were at more risk of relapse than patients in low/intermediate risk group (37%; 95% CI, 11–63 vs 3%; 95% CI, 0–8%; p = 0.0021)
• Outcomes by type of hematologic malignancy
  • OS was higher in patients with MDS than AML (85%; 95% CI, 71–100 vs 70%; 95% CI, 47–100, respectively) and even higher for MPD (91%; 95% CI, 82–100)
  • Relapse rate was also lower in patients with MDS vs AML (14%; 95% CI, 0–30 vs 27%; 95% CI, 1–54; p = 0.02) and even lower in MPD (0%; 95% CI, 0–0)
• OS and NRM was improved irrespective of patients age and HCT-CI score

Conclusion

Myeloablative fractionated busulfan plus fludarabine reduced the incidence of severe acute and chronic GvHD to less than 10% in older patients with hematological malignancies without increasing relapse rates or NRM.

This abstract was considered to be among the three best of TCT by the jury.

Abstract 39: Targeted conditioning with anti-CD45 iodine (131I) apamistamab (Iomab-B) leads to high rates of allo-transplantation and successful engraftment in older patients with active, R/R AML after failure of chemotherapy and targeted agents: preliminary midpoint results from the prospective²

The authors of the abstract evaluated iodine (131I) apamistamab as a conditioning treatment option that would allow to increase rates of CR and to make allo-HSCT more accessible for older patients with active, R/R AML.

In this phase III SIERRA trial (NCT02665065), patients were randomized to receive iodine (131I) apamistamab (Day -12) followed by fludarabine and total body irradiation and allo-HSCT, or conventional care (CC) salvage therapy.

Patient characteristics

• Median age was 64 years
• Patients were heavily pre-treated, with 85% of patients who failed ≥2 induction therapies and 33% who failed targeted therapies

Results

• Preliminary results on 75 (50%) patients are available
• In the experimental arm, 31/31 patients who received iodine (131I) apamistamab were able to undergo allo-HSCT
• In the conventional care arm
  • Out of 38 patients, 31 (82%) failed salvage therapy, even though 12 had received targeted therapies
    • 22 of those patients subsequently crossed to the iodine (131I) apamistamab arm despite high blast cell counts (medium 35% bone marrow blast cells)
• In total, 68% (51/75) of all patients underwent transplantation, including patients who crossed over to iodine (131I) apamistamab after conventional salvage therapy failure
• Iodine (131I) apamistamab was generally well-tolerated, with only one Grade 3 transfusion reaction
• Engraftment was successful in all patients who received iodine (131I) apamistamab
• Non-relapse transplant related mortality in the iodine (131I) apamistamab arm was 3%
• No iodine (131I) apamistamab related deaths were recorded at Day 100

Conclusions

The preliminary results suggest that iodine (131I) apamistamab treatment is suitable for heavily pre-treated older patients with AML, with all patients in the iodine (131I) apamistamab arm achieving CR and undergoing allo-HSCT compared to 18% in the CC arm. We need to await the final report from the study to evaluate whether the promising effect of iodine (131I) apamistamab will be seen in the rest of patients in the investigational treatment arm.

Other key abstracts from the TCT 2020 meeting

Other important abstracts mentioned in the webinar already covered on the AML Hub are listed in the table below

Table 1. Other TCT meeting 2020 highlight abstracts