Cancer Treatment Today

I considered literature CAR-T and also to aplastic anemia, which has the same mechanism, autoimmune suppression of platelet production.

A phase II trial included 25 patients with immunosuppression-refractory aplastic anemia who received eltrombopag at a dose of 50 mg, that was raised up to the maximum 150 mg daily in all but one patient, for a total of 12 weeks. Nine patients achieved a platelet rise of 20,000 cells/mm3 or more above baseline or independence from platelet transfusions for at least 8 weeks if previously transfusion-dependent. Two patients had a red cell response, with an increase in hemoglobin by 1.5 g/dL or more over pretreatment levels below 9 g/dL without transfusion of packed red cells or a reduction by at least 4 units transfused for 8 consecutive weeks. Four patients had a neutrophil response. Eight maintained a response without relapse for a median of 10 months. and six had a response in all three lineages.
These are promising results but the exchange of letters that followed the publication of this study drew attention to the potential risk of inducing progression to myelodysplastic syndromes or acute myeloid leukemia that needs to be considered in patients with aplastic anemia. There are reports of progression to acute myeloid leukemia in patients with myelodysplastic syndromes who are treated with romiplostim, another thrombopoietic, but the relative risk has not been defined.
However, subsequent literature supports such use., and multiple studies have been published.

Promacta is indicated for Severe aplastic anemia (SAA):
• First-line treatment: Promacta is indicated in combination with standard immunosuppressive therapy for adults and children aged 2 years and older with severe aplastic anemia.
• Refractory SAA: Promacta can also be used to treat patients with SAA who have not responded sufficiently to previous immunosuppressive therapy

For thrombocytopenia after CAR-T, there is not an FDA indication; however studies have been supportive, but some recommend further studies. Wesson et al writes: “ The use of eltrombopag for post-CAR T leukopenia and thrombocytopenia was considered safe without any significant toxicities. The use of eltrombopag for post-CAR T cytopenias might be effective in a high-risk patient population but requires further study. “
A 2023 review article in Blood concluded that: “In this first of its kind real-world experience, use of eltrombopag for post-CAR T leukopenia and thrombocytopenia was considered effective in recovery of counts and prevention of bleeding in a high-risk patient population. The use of eltrombopag for post-CAR T cytopenias was considered safe without any significant toxicities of thrombosis or myelodysplasia.”.
Maria-Eva Mingot-Castellano et al concluded similarly.
In conclusion, although not specifically FDA approved and off label, Promacta is medically necessary for CAR-T induced thrombocytopenia even in first line.

Matthew J. Olnes, M.D., Ph.D., Phillip Scheinberg, M.D., Katherine R. Calvo, M.D., Ronan Desmond, M.D., Yong Tang, M.D., Ph.D., Bogdan Dumitriu, M.D., Ankur R. Parikh, M.D., Susan Soto, B.S.N., Angelique Biancotto, Ph.D., Xingmin Feng, M.D., Ph.D., Jay Lozier, M.D., Ph.D., Colin O. Wu, Ph.D., Neal S. Young, M.D., and Cynthia E. Dunbar, M.D.Eltrombopag and Improved Hematopoiesis in Refractory Aplastic Anemia. N Engl J Med 2012; 367:11-19July 5, 2012
Olnes MJ, Scheinberg P, Calvo KR, et al. Eltrombopag and improved hematopoiesis in refractory aplastic anemia. N Engl J Med 2012;367:11-19[Erratum, N Engl J Med 2012;367:284.Metcalf D “A promising new treatment for refractory aplastic anemia” N Engl J Med 2012; 367: 74-75. See letters at: http://www.nejm.org/doi/full/10.1056/NEJMc1209254

CAR-T induced thrombocytopenia:
Promacta, Prescribing Information 2024

Wesson W, Ahmed N, Rashid A, Tabak C, Logan E, Marchena-Burgos J, Nelson M, Davis JA, McGann M, Shune L, Hoffmann M, Abdallah AO, Hashmi H. Safety and efficacy of eltrombopag in patients with post-CAR T cytopenias. Eur J Haematol. 2024 Apr;112(4):538-546. doi: 10.1111/ejh.14141. Epub 2023 Dec 3. PMID: 38044594.

W. Wesson et al, Use of Eltrombopag for Post-CAR T Cytopenias: A Multi-Institutional Experience. Blood (2023) 142 (Supplement 1): 2136.

Mingot-Castellano ME, Reguera-Ortega JL, Zafra Torres D, Hernani R, Lopez-Godino O, Guerreiro M, Herrero B, López-Corral L, Luna A, Gonzalez-Pinedo L, Chinea-Rodriguez A, Africa-Martín A, Bailen R, Martinez-Cibrian N, Balsalobre P, Filaferro S, Alonso-Saladrigues A, Barba P, Perez-Martinez A, Calbacho M, Perez-Simón JA, Sánchez-Pina JM, On Behalf Of The Spanish Group Of Hematopoietic Transplant And Cell Therapy Geth-Tc. Use of Eltrombopag to Improve Thrombocytopenia and Tranfusion Requirement in Anti-CD19 CAR-T Cell-Treated Patients. J Clin Med. 2024 Aug 28;13(17):5117. doi: 10.3390/jcm13175117. PMID: 39274330; PMCID: PMC11396136.