Dr. Zhihui Li
Medical (Hematology) Research Center, Beijing Gaobo Bo Ren Hospital.
Relapse/refractory (R/R) has always been a difficult point in the clinical treatment of malignant hematological tumors. Hematopoietic stem cell transplantation (HSCT) is an important treatment for these patients to achieve long-term survival. Subsequent maintenance treatment is essential to consolidate the effects of HSCT and prevent disease recurrence. Therefore, researchers have been focusing on optimizing the specific maintenance treatment plan for a long time.
The 49th annual meeting of the European Blood and Marrow Transplantation Society (EBMT) will be held in Paris, France from April 23rd to 26th. A study from the Beijing Gaobo Medical (Hematology) Research Center, Beijing Gaobo Bo Ren Hospital by Dr. Tong Wu and her team, specifically focuses on the selection of maintenance treatment plans for R/R malignant hematological patients after allogeneic hematopoietic stem cell transplantation. Dr. Zhihui Li shared her comment of this study.
P268 A real-world study of lenalidomide combined with low-dose venecla in maintenance therapy after allogeneic hematopoietic stem cell transplantation for recurrent and refractory hematological malignancies
Background:
HSCT is the only option for curing R/R malignant hematological patients. However, many patients still relapse after HSCT treatment. Thus, we conducted a retrospective study analyzing the recurrence and survival of patients receiving lenalidomide combined with low-dose venecla as maintenance therapy after HSCT.
Methods:
Retrospectively analyzed 141 patients treated with HSCT from August 2019 to April 2022 at Beijing Gaobo Bo Ren Hospital. Post-HSCT, 119 patients did not receive any maintenance treatment, while 22 did. The median time for patients to receive maintenance treatment was 5 months (1-40 months) after transplantation. Lenalidomide dosages were 5mg/d for children weighing less than 25kg, and 10mg/d for children weighing over 25kg or adults. Venecla dosage was 10mg/d, taken orally. The median follow-up time was 22.4 months (95%CI:17.5~25.7 months).
Results:
Of the 22 patients who received maintenance treatment, 2 died from recurrence. After lenalidomide treatment, 8 (34.8%) patients developed aGVHD, 2 of which were in stages III-IV and remitted after discontinuing medication and undergoing anti-GVHD treatment. 12 developed infections, all effectively treated with antibiotics. Grade 2 adverse events (AE) occurred, but no ≥3 level AE events were observed. All toxic events were tolerable and reversible. Lenalidomide combined with venecla significantly extended the recurrence-free and survival time of patients in the TBI/FLU group (P=0.05; P=0.039).
Conclusion: In this study, lenalidomide combined with venecla as maintenance treatment after HSCT significantly improved the prognosis of patients using the TBI/FLU pre-treatment plan. These results need to be further explored in future prospective clinical trials with larger samples.
Researcher’s Interpretation
1. Why is R/R malignant hematological tumor treatment difficult?
Li Zhihui: R/R malignant hematological tumor treatment in clinical practice is very tricky. The main challenges include patients often being insensitive to chemotherapy treatment or even being primarily drug-resistant; such patients frequently relapse shortly after chemotherapy remission; achieving minimal residual disease (MRD) negative complete remission (CR) after subsequent treatments is rare; and these patients often have many high-risk factors complicating treatment.
2. Why choose lenalidomide combined with low-dose venecla as a maintenance treatment plan?
Li Zhihui: Not all patients can screen for fusion genes and mutation genes at the onset of the disease, and even if they can, there might not always be a targeted drug available. Lenalidomide is a new type of immunomodulatory drug, which has various functions like immunomodulation, anti-tumor, and anti-angiogenesis. Venecla is a BCL-2 inhibitor that promotes the natural apoptosis of tumor cells. Together, they synergize to eradicate tumor cells, maintaining long-term remission after transplantation.
3. How does this plan perform in terms of safety?
Li Zhihui: Known for causing graft versus host disease (GVHD), activated donor T lymphocytes attack normal tissues in patients after transplantation. When using lenalidomide, the GVHD reaction also needs to be monitored
closely, as noted in the research. However, the adverse reactions caused are mild and reversible, and they are well-tolerated overall.
4. What is the prospect of this maintenance plan in future clinical trials?
Li Zhihui: Our real-world study indicates that the combination of lenalidomide and venecla can be an effective maintenance treatment after transplantation for patients with R/R hematological malignancies. However, these are just preliminary results. We need larger samples and more rigorous prospective clinical trials to draw more definitive conclusions.
