Pharmacy SIG Literature Update: A review of BMT CTN1703

In this month’s Pharmacy SIG Literature Update: A review of BMT CTN1703, abatacept for treatment of steroid-refractory GVHD, ECP for GVHD prophylaxis, and more!

Literature summaries are provided as information only. Please refer to the original published articles for complete details on study methodology, results and discussion.

***        Must read. Landmark publication that affects practice

**           Recommend reading. Secondary paper that adds to literature Consider reading.

  • Cursory importance to the practice

Autologous Stem Cell Transplantation

*Bashir Q, Nishihori T, Pasquini MC, Martens MJ, Wu J, Alsina M, Anasetti C, Brunstein C, Dawson P, Efebera Y, Gasparetto C, Geller N, Giralt S, Hall AC, Koreth J, McCarthy P, Scott E, Stadtmauer EA, Vesole DH, Hari P. A Multicenter Phase II, Double-Blind, Placebo-Controlled Trial of Maintenance Ixazomib After Allogeneic Transplantation for High-Risk Multiple Myeloma: Results of the Blood and Marrow Transplant Clinical Trials Network 1302 Trial. Transplant Cell Ther. 2023;29(6):358.e1-358.e7. PMID: 35840087. https://pubmed.ncbi.nlm.nih.gov/35840087/

  • Randomized phase 2, double-blinded, multicenter trial of maintenance ixazomib vs placebo after matched related or unrelated alloHCT in high-risk MM patients (n=57) aged 18-70 years old.
  • Patients received a conditioning regimen with fludarabine, melphalan, and bortezomib; initial patients (n=17) also received bortezomib on days +1, +4, and +7 after transplant. GVHD prophylaxis consisted of tacrolimus and methotrexate. Between day +60 and +120, patients were randomized to receive ixazomib maintenance or placebo for a total of up to twelve 28-day cycles.
  • Fifty-two patients (91%) underwent alloHCT and 43 patients (82.7%) proceeded to randomization to ixazomib (n=21) or placebo (n=22). Baseline characteristics were generally similar between the two groups.
  • Nine patients in the ixazomib group and 11 patients in the placebo group achieved a sCR or CR as best response (p=0.890). Cumulative incidence of grade III-IV aGVHD at day +100 was 9.5% vs 0% (p=1.00). Cumulative incidence of cGVHD at 21 months was 68.6% vs 63.6% (p=1.00). There were no significant differences observed for PFS or OS.
  • The authors conclude that fludarabine/melphalan/bortezomib is a viable conditioning regimen for MM patients, though there is no indication that ixazomib maintenance improves outcomes.

*Spinner M, Sica RA, Tamaresis J, et al. Improved outcomes for relapsed/refractory Hodgkin lymphoma after autologous transplantation in the era of novel agents. Blood. 2023;141(22):2727-37. https://pubmed.ncbi.nlm.nih.gov/36857637/

  • Retrospective, single-center evaluation of outcomes and practice patterns for patients with R/R cHL who underwent autologous HSCT at Stanford Hospital from 2011-2020 (N=183) compared to 2001- 2010 (N=159) using a uniform conditioning regimen of gemcitabine, vinorelbine, carmustine, etoposide, and cyclophosphamide (GN-BVC).
  • Frontline therapy differed with increasing use of ABVD and decreasing use of Stanford V in the modern era (P < 0.001). More patients in the modern era received at least 2 salvage regimens before HSCT (P = 0.022) with choice of agent showing significantly decreased platinum-based chemotherapy and increased use of brentuximab and/or PD1 inhibitors in the modern era (P < 0.001).
  • OS was 89.1% in the modern era vs. 79.0% (HR 0.53, P = 0.011) and PFS was 73.1% vs. 63.3% (P = 0.11). Among patients in a PR at time of HSCT, OS was 88.2% in the modern era vs. 74.6% (P = 0.042).
  • Early NRM was similar between the eras. Most patients died from progressive disease in both eras.
  • This study demonstrates improved survival for R/R cHL after AHCT in the modern era attributed to more effective salvage regimens allowing for better disease control pre-AHCT and improved outcomes for patients who progressed after AHCT. Excellent outcomes were observed with PD-1 inhibitor-based salvage regimens pre-AHCT and support a randomized trial evaluating immunotherapy in the second line setting.

Allogeneic/Haploidentical Stem Cell Transplantation

***Bolaños-Meade J, Hamadani M, Wu J, et al. Post-Transplantation Cyclophosphamide-Based Graft- versus-Host Disease Prophylaxis. N Engl J Med. 2023;388(25):2338-2348. https://pubmed.ncbi.nlm.nih.gov/37342922

  • Phase III, multicenter trial comparing GVHD prophylaxis regimens PTCy/FK/MMF (n=214) and FK/MTX (n=217) following a reduced intensity or nonmyeloablative allogenic peripheral blood stem cell transplant for the treatment of a hematologic malignancy.
  • The median age of participants was 66 years and baseline patient, transplant, and donor-specific characteristics were comparable between the two arms.
  • Primary endpoint: one-year adjusted GRFS was 52.7% (95% CI: 45.8-59.2) compared to 34.9% (95% CI: 28.6-41.3) in the PTCy/FK/MMF and FK/MTX arms, respectively.
  • Secondary endpoints: the cumulative incidence of grade III-IV aGVHD at day 100 and one-year cGVHD was 6.3% (95% CI: 3.5-10.2) and 21.9% (95% CI: 16.4-27.9) versus 14.7% (95% CI: 10.3-19.8) and 35.1% (95% CI: 28.7-41.6) favoring the PTCy/FK/MMF cohort. Survival outcomes including one- year OS, DFS, and transplant-related deaths were comparable between the two groups.
  • Approximately 50% of patients in both arms developed an infection with the incidence of grade II-III infections at one year higher in the PTCy/FK/MMF group at 40% compared to 30.4% in the FK/MTX group, albeit driven primarily by grade II infections. The one-year cumulative incidence of relapse and progression was 20.8% (95% CI: 15.5-26.7) and 20.2% (95% CI: 15-25.9) in the PTCy/FK/MMF and FK/MTX arms, respectively.
  • The authors concluded that while the PTCy/FK/MMF arm reported a higher incidence of infections, patients treated with this triple immunosuppressant regimen experienced longer GFRFS and lower rates of severe aGVHD and of cGVHD.

***Koshy AG, Kim H, Liegel J et al. Phase 2 clinical trial evaluating abatacept in patients with steroid- refractory chronic graft-versus-host disease. Blood. 2023;141(24):2932-43. https://pubmed.ncbi.nlm.nih.gov/36862975/

  • Phase 2 study to evaluate the efficacy of abatacept in steroid-refractory cGVHD. 39 patients were treated with abatacept 10 mg/kg IV every 2 weeks (x3 doses), then every 4 weeks (x3 doses) for a total of 6 doses.
  • At baseline, 46% of patients had moderate disease, 54% had severe disease, and 49% had involvement of at least 4 organs. Organ involvement was skin (85%), mouth (44%), eyes (72%), GI (15%), liver (23%), lung (56%), joints (82%).
  • At baseline, patients were on a median of 2 other immunosuppressive agents: steroids (97%), CNI (44%), MMF (18%), ruxolitinib (10%), aldesleukin (3%). No participants had received ibrutinib or belumosudil.
  • 58% of patients achieved an overall PR. Sites with greatest improvement were lung (57%), liver (54%), GI (50%), mouth (42%). 3-year OS was 72% and FFS was 66%.
  • Most common adverse events were neutropenia, fatigue, headache, and URTIs.
  • Abatacept may be a promising alternative agent in settings in which the currently approved drugs are not tolerated because of their side effect profile or lack of efficacy. Future studies exploring combination strategies with abatacept and the other currently approved drugs for cGVHD have the potential to capitalize on the different mechanisms of actions of the 3 currently approved kinase inhibitors and the immunomodulatory effects of abatacept.

**Bug G, Labopin M, Niittyvuopio R, et al. Fludarabine/TBI 8 Gy versus fludarabine/treosulfan conditioning in patients with AML in first complete remission: a study from the Acute Leukemia Working Party of the EBMT. Bone Marrow Transplant. 2023;58(6):710-716. https://pubmed.ncbi.nlm.nih.gov/37002412/

  • Retrospective study comparing conditioning with fludarabine and fractionated total body irradiation (FluTBI) of 8 Gy (n=137) vs. fludarabine plus treosulfan (FluTreo) 30, 36 or 42 g/m2 (n=617) patients with AML above the age of 40 years undergoing an allogeneic hematopoietic stem cell transplant in first complete remission.
  • Following a propensity score matching to reduce the treatment assignment bias, FluTBI was associated with a significantly lower cumulative incidence of relapse with FluTreo (18.3% vs. 34.7%, p = 0.018) but a higher non-relapse mortality (16.8% vs. 5.3%, p = 0.02) which was observed specifically in patients ≥55 years old. Leukemia free survival and overall survival were similar in the FluTBI and FluTreo groups (64.9% vs. 60.0%, and 66.9% vs. 67.8%) respectively.
  • There was no difference in death due to GVHD between the 2 groups, however infection was the leading cause of death following FluTBI whereas AML recurrence was the predominant cause of death following FluTreo.
  • Authors conclude that FluTBI may be better reserved for younger patients (less than 55 years old) and FluTreo may be preferred in patients with high-risk comorbidities.

*Gaffet M, Wiedemann A, Dalle J-H, et al. Efficacy of haematopoietic stem cell boost as a rescue for poor graft function after haematopoietic stem cell transplantation: A multicentre retrospective study on

behalf of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC). Br J Haematol. 2023;201:1153–1158. https://pubmed.ncbi.nlm.nih.gov/36974355/

  • This was a multicenter, retrospective study that assessed the role of HSC reinjection in post-allo-SCT patients with poor graft function (PGF), defined as lasting cytopenia(s) and/or transfusion dependence for at least two weeks after day +28 without relapse, incomplete donor chimerism, or infectious/drug-related causes.
  • Complete response (CR) was defined as transfusion independence plus recovery of platelets to ≥50 x 109 cells/L, neutrophil to ≥1.5 x 109 cells/L, and hemoglobin to ≥10 g/dL. Partial response (PR) was defined as transfusion independence without meeting laboratory thresholds as defined for CR.
  • 55 patients (median age 14 years [0-66]) were included who had received allo-SCT from various donor sources for a non-malignant condition or hematologic neoplasm, of which 11/55 had a major ABO mismatch.
  • At the time of injection (median of 119 days post-HSC), the median ANC was 1.2 x 109 cells/L, median platelets were 31 x 109 cells/L, and the median hemoglobin was 9.3 g/dL. Pre-boost treatments included GCSF (35 patients), EPO (8 patients), and thrombopoietin analogues (16 patients). At reinjection, the median cell number infused was 5.91 x 106 CD34/kg (IQR: 3.22 -9/15) and 3.14 x 103 CD3/kg (IQR: 0-62.5).

o  Overall response rate (CR and PR) at 1, 3, 6, and 12 months respectively was 67% (39%, 27%), 60% (43%, 17%), 62% (48%, 13%), and 57% (47%, 10%).

  • Two-year OS was 60.7% and de novo aGVHD incidence at D+100 was 3.6%.
  • In a post-trial regression analysis, timing of the boost from transplant and baseline neutrophil and platelet counts were prognostic factors for responsiveness.
  • The authors concluded that donor-derived HSC reinjection may restore hematopoiesis in patients with PGF post-allo SCT.

*Nagler A, Labopin M, Dholaria B, et al. Impact of measurable residual disease on outcomes of unrelated donor haematopoietic cell transplantation with post-transplant cyclophosphamide in AML in first complete remission. Br J of Haematol. 2023;201(6):1169-1178. https://pubmed.ncbi.nlm.nih.gov/36949658/

  • This was a multicenter, retrospective study that assessed the impact of MRD status on post-alloHCT outcomes after a matched unrelated donor (MUD) SCT in adult patients with AML during the first complete remission (CR1). The data originated from registry data submitted to the Acute Leukemia Working Party of the European Society for Bone and Marrow Transplantation (EMBT).
  • 272 patients (107 MRD+, 165 MRD-) were included who had received MUD alloHCT and post- transplant cyclophosphamide (PTCy) based immunosuppressive regimen between July 2010 and June 2021. On average, MRD+ patients were older (54.3 vs. 48.5 years, P = 0.002), were more likely to have a Karnofsky performance status < 90 (33% vs 21.8%, P = 0.045), had fewer patients with adverse cytogenetic risk factors (13.1% vs. 23%, P = 0.013), and were more likely to have received reduced intensity conditioning (RIC) compared to MRD- patients.
  • OS was measured from the time of transplant to death from any cause. Leukemia-free survival (LFS) was defined as survival without relapse or progression. GVHD-relapse-free survival (GRFS) event was defined as the first grade III-IV aGVHD, extensive cGVHD, relapse, or death from any cause. Non- relapse mortality (NRM) was defined as death from any cause without progression or a previous relapse.
  • After a median follow-up of 19 months (16-24), MRD+ patients exhibited a lower 2-year LFS (HR 2.04, 95% CI: 1.23-3.39; P = 0.006), OS (HR 1.83, 95% CI: 1.04-3.25; P = 0.037), and GRFS (HR 1.69, 95% CI: 1.1-2.58; P = 0.016) and higher incidence of relapse at 2 years (HR 2.56, 95% CI: 1.39–4.72) than MRD- patients.
  • No significant between-group differences existed in median time to relapse, NRM, 2-year overall GVHD, 2-year extensive GVHD, or grades II-IV aGVHD at day +180 between the MRD+ and MRD- groups. Neither graft source nor the intensity of the conditioning regimen affected relapse incidence (RI), LFS or OS. Adverse risk cytogenetics was associated with the highest RI and was associated with lower LFS and OS even after adjusting for MRD status.
  • The authors conclude that pre-transplant MRD status may predict 2-year LFS, OS, GRFS, and relapse incidence in patients with AML receiving MUD alloHCT and PTCy. Limitations of the study included a lack of complete genomic information at diagnosis, pre- and post-transplant therapy data, standardized MRD testing methodology, and heterogeneity in conditioning and immunosuppressive regimens.

*Gooptu M, Kim H, Jacobsen E, et al. Favorable outcomes following allogeneic transplantation in adults with hemophagocytic lymphohistiocytosis. Blood Adv. 2023;7(11):2309-2318. https://pubmed.ncbi.nlm.nih.gov/35439287/

  • Retrospective outcomes analysis of 21 adult patients with HLH who were transplanted at Dana- Farber from 2010-2019. Median age was 45 years. Underlying precipitant was documented malignancy in 29%, rheumatologic diagnosis in 14.3%, viral disease in 14.3%, and the remaining with unknown trigger. Initial therapy was largely etoposide-dexamethasone-based or malignancy- directed chemotherapy.
  • 57% of patients had MUD donors, 33% had MRD donors, and 10% had haplo donors. 87.5% of

patients received alemtuzumab “pre-conditioning” stopped at a median of 25 days prior to cell infusion. Conditioning regimen compromised of Flu/Bu (RIC dosing) for MUD/MRD or Flu/Cy/TBI for haplo.

  • 100% of patients engrafted at a median of 15.5 days for neutrophils and 19.5 days for platelets. 3- year OS was 75%, PFS was 71%, relapse rate was 15%, and NRM was 15%.
  • Cumulative Grade 2-4 acute GVHD incidence was 29% at 6 months and 38% at 1 year. Cumulative incidence of moderate-severe chronic GVHD was 29% at 2 years.
  • Authors conclude that RIC HSCT with early administration of alemtuzumab as preconditioning is a potentially curable option for adults with HLH.
  • Mussetti A, Bento L, Bastos-Oreiro M, et al. Role of allogeneic hematopoietic cell transplant for relapsed/refractory aggressive B-cell lymphomas in the CART era. Bone Marrow Transplant.

2023;58(6):673-679. https://pubmed.ncbi.nlm.nih.gov/36918682/

  • Retrospective, multi-center study analysis using the Grupo Español de Trasplante y Terapia Cellular (GETH-TC) registry to compare the clinical outcomes of anti-CD19 CART (n=215) to alloHCT (n=101) from 2016-2020 in patients with diffuse large B-cell lymphoma, not otherwise specified (NOS), primary mediastinal B cell lymphoma, transformed follicular lymphoma, high-grade B cell lymphoma with MYC rearrangements plus BCL2 and/or BCL6, and high-grade B-cell lymphoma-NOS following ≥ 2lines of therapy.
  • CAR-T patients were older compared to alloHCT (p<0.01), had higher R-IPI score (p<0.01), primary refractory disease at diagnosis (p<0.01) and worse ECOG (p<0.01).
  • Progression free survival and overall survival were similar between both groups (p=0.75 and p=0.12 respectively) as well as relapsed disease/ progression of disease (p=0.23) however CAR-T was associated with lower non-relapse mortality (p=0.02).
  • Authors conclude that CAR-T should be favored to alloHCT due to the reduced toxicity profile and similar survival outcomes.

*Socie G, Niederwieser D, von Bubnoff N, et al. Prognostic value of blood biomarkers in steroid- refractory or steroid-dependent acute graft-versus-host disease: a REACH2 analysis. Blood.

2023;141(22):2771-9. https://pubmed.ncbi.nlm.nih.gov/36827620/

  • Analysis of the utility of models developed utilizing various markers that were collected at baseline and Day 14 during the REACH2 trial (ruxolitinib vs. BAT for acute GVHD).
  • Baseline data consisted of 295 eligible patients for any of the 21 biomarkers of interest (ruxolitinib = 149, BAT = 118) and were included in the day 14 data set. Patients who did not receive day 28 biomarker samples were not included.
  • A total of 29 biomarkers were assessed in samples collected at baseline and at day 14 of treatment. Biomarkers were categorized into 3 classes: aGVHD-associated cytokines/chemokines, immune cells, or inflammatory proteins. 21 were included in the final analysis and compared in responders and non-responders regardless of treatment regimen.
  • Approximately 1/3 of markers had significantly higher expression in non-responders than in responders at both baseline and day 14.
  • Lower levels of most aGVHD markers at baseline were associated with an increased probability of response. Treatment with ruxolitinib, conditioning, skin involvement, and age were strongly associated with increased likelihood of response in at least one model.

*Konuma T, Matsuda K, Shimomura Y, et al. Effect of graft-versus-host disease on post-transplantation outcomes following single cord blood transplantation (CBT) compared with haploidentical transplantation with post-transplantation cyclophosphamide for adult acute myeloid leukemias.

Transplant Cell Ther. 2023 Jun;29(6):365.e1-365.e11. https://pubmed.ncbi.nlm.nih.gov/36889507/

  • Retrospective study of 1,981 patients aged 16-65 across >300 HCT centers in Japan receiving single- unit unrelated CBT (n= 1691) or haploidentical HCT using PTCy-based GVHD prophylaxis (n= 290) between 2014 and 2020 to compare the effect of aGVHD and cGVHD on post-transplantation outcomes in AML.
  • The CBT group had a higher proportion of females, non-CR status at HCT, myeloablative conditioning regimens, GVHD prophylaxis based on calcineurin inhibitors and methotrexate, and positive anti- HLA antibody status.
  • Cumulative incidences of grade I-II and grade III-IV aGVHD at 100 days were significantly higher in CBT vs PTCy-haplo-HCT recipients (48.6% vs 41.0%, p= 0.018, for grade I- II acute GVHD; 13.0% vs 6.9%, p= 0.001 for grade III-IV aGVHD); cumulative incidence of limited cGVHD at 2 years was also significantly higher with CBT (17.7% vs 13.2%, p= 0.043), but extensive cGVHD was comparable (11.4% vs 14.3%).
  • In univariate analysis the OS was significantly improved in those who developed grade I-II acute GVHD (p< 0.001) and limited chronic GVHD (p< 0.001) among CBT recipients, but was not significant among PTCy-haplo-HCT recipients; in multivariate analysis treating GVHD as a time-dependent covariate, grade I-II acute GVHD impact on reducing overall mortality differed significantly between CBT and PTCy-haplo-HCT (CBT HR 0.73, 95% CI, 0.60 to 0.87; PTCy-haplo-HCT HR 1.07; 95% CI  0.70 to 1.64; p= 0.038).
  • The authors conclude that grade I-II aGVHD was associated with a significant improvement in overall survival in adults with AML receiving CBT but not haploidentical HCT with PTCy-based GVHD prophylaxis.

*Li J, Wang Y, Zhang Y, et al. Hematopoietic stem cell transplantation for hepatitis-associated aplastic anemia and non-hepatitis-associated aplastic anemia: A propensity score-matched analysis. Br J Haematol 2023; 201:1179-1191. https://pubmed.ncbi.nlm.nih.gov/36994699/

  • This was a retrospective analysis of 260 patients who received HSCT for acquired aplastic anemia (AA) at a 766-bed tertiary hospital in Tianjin China to compare transplant outcomes and immune reconstitution in patients with hepatitis-associated AA (HAAA) vs non-HAAA. A subset analysis was also conducted to compare safety and efficacy of matched sibling donor (MSD) HSCT vs haploidentical (HID) HSCT in this patient population.
  • HAAA was defined as a variant of AA in which pancytopenia occurred concurrently or within 6 months of an increase in hepatic transaminases above 5 times the upper limit of normal. The serological and virological parameters of hepatitis A, B and C were negative.
  • From January 2014 to August 2022, 30 patients with HAAA and 230 patients with non-HAAA were identified. Propensity score-matched (PSM) analysis was conducted to minimize the impact of potential unbalanced variables between the two groups reducing the comparator non-HAAA population to 90 patients for the final analysis.
  • All patients received a conditioning regimen of anti-thymocyte globulin (ATG), cyclophosphamide, fludarabine + busulfan and a GVHD prophylaxis regimen of cyclosporine or tacrolimus plus methotrexate + mycophenolate mofetil. All patients received filgrastim from day + 6 until ANC recovery defined as an ANC ≥ 0.5 x 109 cells/L for three consecutive days post-transplant without G- CSF.
  • The donor type was comparable between the PSM matched cohorts (57% HID and 43% MSD in the HAAA cohort vs 40% HID and 60% MSD in the non-HAAA cohort). The donor source was predominately peripheral blood stem cells in both cohorts (83.3% vs 82.2%). All other patient characteristics in the PSM matched cohorts were non-significant.
  • No differences were found in the transplant outcomes between the PSM matched cohorts of HAAA and non-HAAA patients in the estimated 5-year overall survival rate (75.8% vs 86.5%, p=0.409), failure-free survival (FFS) rate (74% vs 83.2%, p=0.485), GVHD-free FFS rate (61.2% vs 67.6%, p=0.669), engraftment, post-transplant severe infection, CMV or EBV viremia, or GVHD incidence and had similar patterns of immune reconstitution. In the subset analysis based on HID vs MRD donor type no difference existed in survival, transplant-related mortality or GVHD cumulative incidence.
  • The authors conclude that transplant outcomes of HAAA patients were comparable to those of non- HAAA patients after balancing potential confounders with PSM. A smaller subset analysis suggests that HID HSCT can be a valid transplant option for HAAA patients.

CAR-T Therapy

**Dong N, Lopes-Garcia LR, Vinal D, et al. Outcomes of CD19-directed chimeric antigen receptor T cell therapy for transformed non-follicular lymphoma. Transplant Cell Ther. 2023 Jun;29(6):349.e1-349.e8 https://pubmed.ncbi.nlm.nih.gov/36878427/

  • Single-center retrospective study of 136 CAR-T treatments (111 with axi-cel and 25 with tisa-cel) in 134 patients outside a clinical trial from November 2017 to May 2021 at Moffitt Cancer Center to evaluate the outcomes of axi-cel and tisa-cel in transformed non-follicular lymphoma tNFL which includes transformed marginal-zone lymphoma (tMZL) and transformed chronic lymphocytic leukemia and small lymphocytic leukemia (tCLL/SLL) patients not included in respective pivotal studies; 90 with de novo DLBCL/PMBCL, 23 with tFL, and 21 with tNFL (12 tMZL and 9 tCLL/SLL).
  • Among a total of 136 CAR-T treatments, ORR and CR for tCLL/SLL were 66.7% and 55.6%, respectively, and 92.9% and 71.4% for tMZL; no difference was observed between tNFL and DLBCL/tFL for any efficacy or survival outcomes, though survival estimates largely have not matured yet.
  • The tNFL patients were more likely to have ICANS (p= 0.04) and receive tocilizumab (p= 0.01) than DLBCL/tFL patients, and two tNFL patients died of treatment-related toxicity after axi-cel; compared to tisa-cel, axi-cel was associated with greater any-grade ICANS (50.5 vs 20.0%; p< 0.01), grade ≥3 ICANS (25.2% vs 4.0%; p= 0.02), and steroid use (42.3% vs 16.0%; p= 0.01).
  • Six patients (five with tCLL/SLL and one with tMZL) received concurrent ibrutinib throughout apheresis, lymphodepletion, and following tisa-cel infusion; all tolerated treatment with only one patient having transient grade ≥3 CRS and ICANS and four of six in remission at last follow-up (6.8 to 27.2 months duration).
  • The authors conclude that data supports the use of CD19 CAR-T and concurrent ibrutinib therapy in the tNFL population, with comparable response to other LBCL histologic types and the potential to induce durable remission in tCLL/SLL and tMZL patients who have failed multiple prior lines of therapy.

Supportive Care

*Bloch EM, Focosi D, Shoham S, et al. Guidance on the Use of Convalescent Plasma to Treat Immunocompromised Patients With Coronavirus Disease 2019. Clin Infect Dis. 2023;76(11):2018-2024. https://pubmed.ncbi.nlm.nih.gov/36740590

  • Current consensus and best practices guiding the optimal dose, frequency/schedule and duration of CCP for the treatment of COVID-19 in immunocompromised patients are lacking. CCP is a valuable treatment option, especially early in the infectious course, for immunocompromised individuals due to its polyclonal composition, allowing it maintain efficacy against SARS-CoV-2 variants. CCP may be included in the armamentarium of therapeutic options either alone or in combination with an antiviral for acute COVID-19 as well as for the treatment of protracted COVID-19.
  • There is an absence of data to recommend the optimal antiviral regimen: CCP alone or combined with an antiviral medication. Dual therapy may not be feasible due to eligibility for use of antivirals such as nirmatrelvir/ritonavir and molnupiravir. For patients admitted to the hospital for persistent COVID-19, the group suggests remdesivir plus one unit of CCP every other day x3 units total may be a feasible treatment regimen.
  • While the optimal dose, duration and frequency remains unclear, acute COVID-19 may be treated with one to two units of CCP with additional doses guided by clinical response. In the case of persistent COVID-19 with very high viral loads, CCP should be given at defined intervals until evidence of viral clearance.
  • Cycle thresholds can be used to determine the treatment effect of CCP on viral load and subsequently guide additional CCP therapy when lab monitoring of SARS-CoV-2 viral loads may not be possible. The group acknowledges that the optimal timing and frequency of monitoring cycle threshold values is unknown; however, for stable patients, it is reasonable to check a cycle threshold 5-7 days after CCP.
  • Several challenges exist with using CCP. First, the composition of CCP varies amongst products limiting the ability to determine if any units are of similar dose and efficacy. Second, lack of reliable supply and a supply containing Group B and AB plasma may restrict the patients who can receive CCP. Last, CCP products are not matched temporally or geographically based on the circulating variants likely limiting the efficacy of the product.
  • At present, there are a paucity of data, especially robust clinical trials, surrounding CCP use in immunocompromised patients and consensus guidelines to recommend its use. However, the authors recommend CCP to treat acute and protracted COVID-19 infections in immunocompromised individuals and call for the reevaluation of regulatory donation requirements of CCP to increase its availability to patients in need.

*Ali MM, Gedde-Dahl T, Osnes LT, et al. Extracorporeal photopheresis as graft-versus-host disease prophylaxis: a randomized controlled trial. Transplant Cell Ther. 2023 Jun;29(6):364.e1-364.e11. https://pubmed.ncbi.nlm.nih.gov/36878428/

  • A randomized open-label trial of 157 adults (age 18-74 years) receiving first allogeneic HCT for a hematologic malignancy to assess whether ECP post-transplantation could prevent GVHD within the first year of transplantation.
  • Control group patients (n= 81), receiving drug-based prophylaxis as cyclosporine in combination with methotrexate on days +1, +3, +6, and +11, mycophenolate mofetil on days 0 to +28, or sirolimus days -1 to +2; the intervention group (n=76) received the same prophylaxis as control plus ECP directly on engraftment followed by twice weekly for 2 weeks, then once weekly for 4 weeks.
  • During the first year, 45 ECP patients and 52 control patients developed GVHD (HR 0.82; 95% CI, 0.55 to 1.22; p= 0.32), with no differences in acute or chronic GVHD or its organ distribution.
  • Nearly half of the ECP group (33 of 76) discontinued intervention before completing all planned sessions due to GVHD, long distance, or practical problems; per-protocol analysis showed a significant difference in any-grade GVHD between the ECP group (n=39) and control group (n=77) of 46% vs 68%, respectively (HR 0.47; 95% CI, 0.27 to 0.80; p= 0.006).
  • There was no significant difference in any survival outcomes or in immune reconstitution between the groups.
  • The authors conclude that the first intention-to-treat RCT using ECP as GVHD prophylaxis does not support ECP as an adjunct to standard drug-based GVHD prophylaxis.

ASTCT Pharmacy SIG Research Working Committee:

Amber Clemmons, Jennifer Collins, Aaron Cumpston, Arpita Gandhi, Alycia Hatashima, Haval Norman, Thomas Hughes, Jitesh Kawedia, Kaily Kurzweil, Andrew Lin, Dennis Marjoncu, Cameron Ninos, Mary Nauffal, Jonathan Ptachcinski, Julianna Roddy, Justin Tossey, Sorana Ursu, Abhijna Vithal Yergolkar

Please consider joining the pool of content reviewers for the Pharmacy SIG. Throughout the year the various working committees frequently need content reviewers for slides, manuscripts, and other materials and your expertise would be invaluable.  Click here to apply!

Tags: Pharmacy SIG, CAR-T, MRD, AlloHCT, GVHD, Outcomes, Lymphoma, leukemia, Pharmacy, cGVHD, aGVHD, COVID19, PTCy, CART, PTC, mismatched donor, survival rate, acute myeloid leukemia

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