Post-Conference Perspectives: Advances in the Management of Newly Diagnosed Ph+ Acute Lymphoblastic Leukemia - Episode 5

Notable Advancements in Treatment for ALL

,

Key advances in ALL treatment from ASCO 2023 are discussed by Dr Przespolewski.

Ibrahim Aldoss, MD: Dr Przespolewski, can you discuss some of the most exciting advances in acute lymphoblastic leukemia and other hematological malignancies that were recently presented at ASCO 2023?

Amanda Przespolewski, DO: So, I have a couple that I'd like to discuss.

The first one that I'd like to share with you is abstract number 7006, presented by Dr Matt Wieduwilt and colleagues, which was entitled "Chemotherapy-free Treatment with Inotuzumab Ozogamicin, and Blinatumomab for Older Adults with Newly Diagnosed pH-negative, CD22 Positive, B-Cell Acute Lymphoblastic Leukemia." So, this study sought to enroll patients that were 60 years of age or older, and those patients underwent induction with Inotuzumab following their initial induction course dependent on the degree of debulking that they achieved within their bone marrow. If they were in CR/CRi, they were able to go on to receive further Inotuzumab at a 0.5 mgs per meter squared dosing schema. But if patients did have adequate debulking and did not yet achieve CR/CRi, they got a slightly higher dose of Inotuzumab at 0.8 mgs per meter squared on days one, eight, and 15. If patients did not achieve adequate debulking with one cycle of Inotuzumab, they automatically went on to receive blinatumomab and did not receive any further Inotuzumab at that time. So, the primary endpoint for this study was one year event-free survival with a lower limit of a 90% confidence interval greater than 10%. So, when this abstract was presented, 33 patients had been treated to date with a median age of 71 years and a median white cell count of 3.2. Cumulative complete remission rates through course one with Inotuzumab were 85%, and those rates increased to 97% following course two with blinatumomab. The median follow up of this study was 22 months with a one-year event-free survival of 75%. and that two-sided 90% confidence interval was 63 to 89%, which did meet the primary endpoint. In total, nine patients relapsed, and one patient experienced sinusoidal occlusion syndrome of the liver, and the one-year overall survival was 84%. So, these authors were able to demonstrate that this chemotherapy-free regimen has significant activity in older adults with newly diagnosed pH negative acute lymphoblastic leukemia. And I look forward to more mature survival data. And I'm also interested to know the measurable residual disease status of these patients following treatment.

So next, I would like to move on to Abstract 7000, presented by Dr Claire Roddie and colleagues, entitled "The Safety and Efficacy of Obe-cel AUTO1, a Fast Off-Rate CD19 CAR in Patients with Relapsed or Refractory B-cell Acute Lymphoblastic Leukemia." So, the agent that's being discussed in this clinical trial is an autologous CD19 CAR with a fast off-rate CD19 binding domain, which was designed intentionally to reduce the CAR-T immunotoxicity and to improve persistence of the CAR within circulation. So, this study was an open-label, multi-global, single arm, phase 1B2, study that enrolled patients into three cohorts based on their disease status. Those patients with fully relaxed refractory acute lymphoblastic leukemia with morphologic disease. The second cohort is aiming to study patients that are only MRD positive. And the third cohort is evaluating patients with only extra medullary disease at time of relapse. So, prior to being dosed with CAR-T patients underwent bridging therapy is necessary during the manufacturing process, and then patients underwent lympho depletion with fludarabine and cyclophosphamide. The target dose of the CAR was four times 10 to the six, and it was administered as a split dose on day one and day 10. The primary endpoint for this phase 1B2 study is overall remission rate. And the data that's presented in this abstract does reflect a pre-specified interim analysis of the first 50 patients that were treated in the first cohort, which were those patients with overt morphologic relapse. Those patients were followed for three months, or they were included in this interim analysis if they were discontinued prior to that third month. The median age of patients treated on this study was 50 years with a range of between 20 to 81 years. 42% of these patients had undergone a prior allergenic stem cell transplant, and the median number of lines of therapy in patients enrolled on this study was two. So impressively, the CR/CRi rate was observed to be 70% and the persistence of this product was noted to be ongoing and the majority of patients that were responding at their last follow-up with a median follow-up of 9.5 months. So, with regards to the safety analysis of total of 92 patients at the time of data cutoff were available for safety evaluation. 63% of these patients did develop any grade of CRS, but only 3% developed a grade three or greater CRS. And with respect to CNS toxicity in ICANS, ICANS of any grade was observed in 23% of patients, but only 8% of these patients developed a grade three or greater adverse event. So, the authors of this abstract were able to demonstrate that the obe-cel product for adults with relapsed refractory B-cell ALL is safe. And impressively it had demonstrated lower rates of ICANS in CRS, even in patients with a high burden of disease. Which is important for patients that are older, and this may have more general applicability. This agent is also effective, and I look forward to longer term follow-up of this agent.