The results showed that half of patients had disease relapse by 8.5 months, but once patients made it to allogeneic hematopoietic stem cell transplant, they had prolonged overall survival, with the median not yet reached.5

The study included a subgroup of 18 patients with the genetic abnormality mixed-lineage leukemia (MLL) rearrangement, and the long-term data on these patients may offer insights.5 

“We think that [patients with MLL rearrangement] have more of an ability to lineage switch from ALL to [acute myeloid leukemia],” explained Dr Shahani, who was not involved in the study. She said it will be interesting to see whether these patients develop a myeloid type of leukemia.


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A small expanded access program in Italy in which 16 patients received axicabtagene ciloleucel (axi-cel; Yescarta®) for primary mediastinal B-cell lymphoma (PMBCL) provides preliminary evidence that prior exposure to immune checkpoint inhibitors (ICIs) may not compromise efficacy or safety.6

Patients who were not previously treated with ICIs had an overall response rate of 86% at 30 days, which was similar to the 75% response rate for the group of patients overall. Also, all reports of cytokine release syndrome (CRS) were grade 1 or 2 and nearly all events of neurotoxicity were grade 1 or 2, although 1 patient experienced grade 3 neurotoxicity.7

Data from a managed access program in Spain in which previously treated patients with chronic myeloid leukemia (CML) received asciminib were included in the presentation of the late-breaking phase 3 ASCEMBL clinical trial (ClinicalTrials.gov Identifier: NCT03106779) results at ASH 2020.7,8 The trial results suggested that asciminib may be a new treatment option for patients with Philadelphia chromosome–positive CML in chronic phase who were previously treated with tyrosine kinase inhibitors.9

Lead author of the managed access study Alejandro Luna, MD, hematology and hemotherapy service, Ramón y Cajal Hospital, Madrid, Spain, told Cancer Therapy Advisor that because asciminib is currently commercially unavailable, he considers the results from the modest sample helpful for defining the “future role” of asciminib for patients with CML.

Data from the expanded access study, ZUMA-9 (ClinicalTrials.gov Identifier: NCT03153462), which provided axi-cel to patients with relapsed/refractory large B-cell lymphoma, showed a high patient response rate, confirming the results of the pivotal ZUMA-1 trial (ClinicalTrials.gov Identifier: NCT02348216).10

Insights from compassionate use were also generated by three different research groups for polatuzumab vedotin in diffuse large B-cell lymphoma and from the REMIX study, in which patients with relapsed or refractory multiple myeloma received ixazomib in combination with lenalidomide and dexamethasone.11-14 Researchers in the United States similarly reported expanded access data for crenolanib in 5 children with FLT3-mutant acute myeloid leukemia and for COVID-19 convalescent plasma in 16 cancer patients with COVID-19.15,16

“It’s almost weird to think that these programs were running in the past, providing investigational medicine to patients — and not collecting data from them and not reporting anything on that,” said Tobias Polak, real-world data lead at myTomorrows, a global company that connects patients to expanded access programs and helps pharmaceutical companies collect data from these programs.

Polak, who is also a PhD student at Erasmus University in Rotterdam, the Netherlands, said that the appearance of these data in at the ASH 2020 meeting does not necessarily mean they will be used to support an approval in the future or be submitted to regulatory authorities toward any indication-specific goal.

But, earlier this year, Polak and colleagues reported evidence of regulatory authorities basing drug approvals on expanded access.14 “That’s really a totally different ballgame,” he said.

References

  1. US Food and Drug Administration. Expanded access. FDA.gov. Updated April 27, 2020. Accessed December 21, 2020.
  2. US Food and Drug Administration. Real-world evidence. FDA.gov. Accessed December 21, 2020.
  3. US Food and Drug Administration. Framework for FDA’s real-world evidence program. FDA.gov. Published December 2018. Accessed December 21, 2020.
  4. Reagan-Udall Foundation for the FDA. Leveraging real-world treatment experience from expanded access protocols. Public meeting report. Published November 19, 2018. Accessed December 21, 2020.
  5. Locatelli F, Zugmaier G, Mergen N, et al. Blinatumomab in children with relapsed or refractory B-precursor acute lymphoblastic leukemia (R/R-ALL): Final results of 110 patients treated in an expanded access study (RIALTO). Presented at: the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition; December 5-8, 2020. Abstract 977.
  6. Chiappella A, Dodero A, Guidetti A, et al. Checkpoint inhibition before axicabtagene ciloleucel cell therapy in primary mediastinal B-cell lymphoma (PMBCL) treated in real life setting. Presented at: the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition; December 5-8, 2020. Abstract 3058.
  7. Luna A, Estrada N, Boque C, et al. Safety and efficacy profile of asciminib as treatment in chronic myeloid leukemia patients after several tyrosine-kinase inhibitors failure. Poster presented at: the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition; December 5-8, 2020. Abstract 1241.
  8. Hochhaus A, Boquimpani C, Rea D, et al. Efficacy and safety results from ASCEMBL, a multicenter, open-label, phase 3 study of asciminib, a first-in-class STAMP inhibitor, vs bosutinib (bos) in patients (pts) with chronic myeloid leukemia in chronic phase (CML-CP) previously treated with ≥2 tyrosine kinase inhibitors (TKIs). Presented at: the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition; December 5-8, 2020. Abstract LBA-4.
  9. Lawrence L. STAMP inhibitor may be a new treatment option in CML. Cancer Therapy Advisor. December 8, 2020.
  10. Jacobson CA, Locke FL, David B. Miklos DB, et al. Outcomes of patients (Pts) in ZUMA-9, a multicenter, open-label study of axicabtagene ciloleucel (axi-cel) in relapsed/refractory large B cell lymphoma (R/R LBCL) for expanded access and commercial out-of-specification (OOS) product. Presented at: the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition; December 5-8, 2020. Abstract 2100.
  11. Liebers N, Duell J, Nörenberg D, et al. Polatuzumab vedotin in relapsed and refractory (r/r) large B-cell lymphoma (LBCL): Real-world data of the German national compassionate use program (CUP). Presented at: the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition; December 5-8, 2020. Abstract 1206.
  12. Wu J, Liu Y, Fei L, et al. A multicenter real-life study of polatuzumab vedotin combined with immunochemotherapy in patients with R/R DLBCL: Preliminary data on efficacy and safety in Chinese cohort. Presented at: the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition; December 5-8, 2020. Abstract 2143.
  13. Tsai C, Tien FM, Hou H, et al. Polatuzumab vedotin-based salvage chemotherapy in the third-line or above treatment for diffuse large B-cell lymphoma. Presented at: the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition; December 5-8, 2020. Abstract 3057.
  14. Clement-Filliatre L, Benboubker L, Stoppa A, et al. Real-life-setting effectiveness of ixazomib in combination with lenalidomide and dexamethasone in relapsed or refractory multiple myeloma: The Remix study. Presented at: the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition; December 5-8, 2020. Abstract 1377.
  15. Tarlock K, Meshinchi S, Rubnitz JE, et al. Clinical benefit and tolerability of crenolanib in children with relapsed acute myeloid leukemia harboring treatment resistant FLT3 ITD and variant FLT3 TKD mutations treated on compassionate access. Presented at: the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition; December 5-8, 2020. Abstract 1973.
  16. Ibrahim M, Pal P, Niu A, et al. COVID-19 convalescent plasma decreased oxygen requirement and hospital stay in COVID-19 hospitalized patients including those with hematological malignancies: A report of 16 patients. Presented at: the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition; December 5-8, 2020. Abstract 102.
  17. Polak TB, van Rosmalen J, Uyl–de Groot CA. Expanded Access as a source of real-world data: An overview of FDA and EMA approvals. Br J Clin Pharmacol. 2020;86:1819-1826. doi:10.1111/bcp.14284