Pharmacy SIG Literature Update: Impact of Omitting Post-transplant mini-MTX Post alloHCT

In this month’s Pharmacy SIG Literature Update: impact of omitting post-transplant mini-MTX post alloHCT, haploidentical versus matched unrelated versus matched sibling donor hematopoietic cell transplantation with post-transplantation cyclophosphamide, narsoplimab for the treatment of alloHCT associated thrombotic microangiopathy 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

*Ladbury C, Somlo G, Dagis A, et al. Long-Term Follow-Up of Multiple Myeloma Patients Treated with Tandem Autologous Transplantation Following Melphalan and Upon Recovery, Total Marrow Irradiation. Transplant Cell Ther. 2022;28(7):367.e1-367.e9. https://pubmed.ncbi.nlm.nih.gov/35534000/

  • Due to the increased toxicity of TBI in combination with melphalan for MM, total marrow irradiation (TMI) has been used as a sole ablative modality during the second cycle of tandem autoHCT (TASCT) for MM patients on a phase I-II trial
  • Patients with Durie-Salmon stage I-III MM, age ≤70 years, within 18 months of diagnosis, in CR, PR or with stable disease (SD) received melphalan 200 mg/m2 and ASCT (cycle 1) then after recovery, TMI and another ASCT (cycle 2)
    • Total TMI dose ranged from 1000 to 1800 cGy in 200 cGy increments
    • Maintenance with an immunomodulatory drug and dexamethasone was given for up to 12 months
  • Of the 54 treated patients, 44 received planned TASCT and 10 did not undergo TMI/ASCT due to concerns following melphalan-induced toxicity or due to patient or physician preference
  • Median time between first and second ASCTs on protocol was 65 days (range, 47 to 125 days)
  • Following ASCT and maintenance, CR and VGPR was 48.1% and 22.2%, respectively

·    PFS and OS at 10 years were 20.4% (95% CI, 10.9% to 31.9%) and 38.8% (95% CI, 25.9% to

51.5%), respectively

  • Secondary neoplasms included AML (n = 1), papillary thyroid and prostate carcinoma (n = 1), melanoma (n = 1) and nonmelanoma skin cancers (n = 1)
  • TMI as part of TASCT was well tolerated, and TASCT was associated with a 20.4% PFS plateau
  • Authors conclude that future studies with TMI as a conditioning regimen for MM before ASCT are warranted

Allogeneic stem cell transplantation

*Nagler A, Peczynski C, Dholaria B, et al. Impact of conditioning regimen intensity on outcomes of second allogeneic hematopoietic cell transplantation for secondary acute myelogenous leukemia. Bone Marrow Transplant. 2022;57(7):1116-1123 https://pubmed.ncbi.nlm.nih.gov/35501565/

  • Multicenter study using data registries from the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT) in adult patients at least 18 years of age with secondary AML (sAML) in CR or active disease undergoing second alloHCT was conducted between 2005 and 2019 to compare transplant outcomes between patients received RIC compared with MAC
  • 215 patients were included of which 62% received RIC and 38% received MAC as the preparative regimen. Median patient age was 55.1 and 52.5 years between the RIC and MAC groups. Disease status at HCT2 did not differ between the 2 groups with CR of 40.3% and 40.8% for RIC and MAC, respectively (p = 0.95)
  • The relapse incidence (RI) at two years was 58.3% versus 51.1% in RIC and MAC group, respectively
  • The incidence of 2-year leukemia free survival, GVHD-free RFS, and OS was 26.6% versus 26%, 16.4% versus 12.1%, and 31.4% versus 39.7%, for RIC and MAC groups, respectively. Longer time to relapse after HCT1 and achieving CR before HCT2 were significant prognostic factors in the multivariate analysis for lower RI and improved LFS, OS and GRFS
  • Authors conclude that HCT2 is feasible for patients with sAML that relapse after HCT1 and have reasonable outcomes with a 2-year OS of 30–40% and a LFS of 26%

**Lin A, Brown S, Maloy M, et al. Impact of omitting post-transplant minidose-methotrexate doses in allogeneic hematopoietic cell transplantation. Leuk Lymphoma 2022;63(7):1686-1693. https://pubmed.ncbi.nlm.nih.gov/35142567/

  • Single-center, retrospective review to evaluate the omission of post-transplant MTX in patients who received an alloHCT followed by GVHD prophylaxis with mini-MTX (5 mg/m2 days 1, 3, 6, and 11) and a CNI. MTX doses were held for severe mucositis, pleural effusion or anasarca, substantial worsening of renal function or total bilirubin.
  • A total of 370 patients who received a MRD, URD, or MMUD transplant with MA, RIC, or NMA chemotherapy were evaluated. Patients that had MTX doses omitted were younger (median 61 years versus 52 years), but groups were otherwise similar, with majority of patients in both groups receiving mobilized PBSC (86%).
  • Of the cohort, 50 patients received 1-3 doses of MTX and the most common reason for dose omission was mucositis (54%) followed by hyperbilirubinemia (38%), although many patients had multiple reasons cited (30%). The majority of these patients received MMF (72%), with 11 of them receiving it in combination with corticosteroids. An additional three patients received corticosteroid monotherapy, and the remaining 11 patients received no additional prophylaxis.
  • No increased risk in grade II-IV and III-IV aGVHD was observed in both groups. The 6-month cumulative incidence of grade II-IV aGVHD was 49% with four MTX doses and 62% with omitted MTX doses, and grade III-IV aGVHD was 16% and 17%, in the four MTX dose group versus the omitted MTX dose group, respectively. A significant increase in cGVHD was seen when MTX doses were omitted, HR 2.27 (1.11, 4.61; p=0.24).
  • In the group that MTX was omitted, there was a non-significant decrease in OS. The 1-year OS was 73% in patients who received four doses of MTX versus 57% in those who had doses omitted. After adjusting for age, CIBMTR risk category, and HLA/matching status there was a significant impact on OS (HR 1.61; 95% CI 1.06, 2.45; p = 0.024). There was no significant difference in PFS/RFS, NRM, or GVHD-related mortality.
  • Although the risk of aGVHD was possibly ameliorated by the addition of MMF, a high threshold for omitting any dose of MTX should be maintained and every attempt should be made to complete the full course of therapy.

**Mehta RS, Saliba RM, Ghanem S, et al. Haploidentical versus Matched Unrelated versus Matched Sibling Donor Hematopoietic Cell Transplantation with Post-Transplantation
Cyclophosphamide. Transplant Cell Ther. 2022 Jul. 28(7):e1-e395.

  • Comparison of outcomes in study cohort of all patients with hematologic malignancies who received first alloHCT with PTCy for GVHD prophylaxis between January 2015 and July 2020 at a single institution (n = 661)

o  Haplo (n = 275), MUD (n = 246), and MSD (n = 140)

  • Excluded UCB, manipulated graft, and MMUD
  • Most common diagnoses were AML and MDS
  • Haplo group: younger (median age: 51 years), higher rates of ALL (18%) and CLL (17%), highest proportion of RIC vs. MUD and MSD (76% vs 40% vs 26%, respectively), majority received BM graft (66%) and almost all received Tacro/MMF/PTCy (96%)
  • In multivariate analysis, haplo group was found to have significantly higher NRM (HR 3.2; 95% CI, 2-4.9; P < 0.001) and inferior PFS (HR 1.8; 95% CI, 1.4-2.4; P < 0.001) and OS (HR 2.2; 95% CI, 1.6- 3; P < 0.001) compared with the MUD group
  • Relapse/progression was the most common cause of death in all groups. Among causes of NRM, the haplo group had more infection-related deaths (haplo, 40%; MUD, 26%; MSD, 36%) and fewer GVHD-related deaths (haplo, 18%; MUD, 39%; MSD, 29%) than the other groups
  • Haplo group also had significantly higher risk of grade ≥3 viral infections (P < 0.001), grade ≥3 fungal infections (P = 0.01), grade ≥3 hemorrhagic cystitis (P = 0.003), grade ≥3 cardiovascular toxicities (P = 0.03), and slower reconstitution of CD4, CD8, and regulatory T cells but faster reconstitution of NK cells
  • Authors concluded based on the data that even with the use of PTCy, the outcomes of haploHCT are inferior to those of HLA-matched donor HCT

    **Kutze JL, Merten JA, Pawlenty AG, et al. Relationship of iothalamate clearance and NRM in patients receiving fludarabine and melphalan reduced-intensity conditioning. Blood Advances. 2022; 6(3):3844- https://ashpublications.org/bloodadvances/article/6/13/3844/485185/Relationship-of-iothalamate- clearance-and-NRM-in. PMID: 35522968.

  • Single-center, retrospective cohort study to identify the relationship between pre-transplant kidney function estimated by measured GFR (mGFR) and post-transplant outcomes, particularly NRM. Included were adult patients who received an alloHCT with fludarabine + melphalan conditioning from January 2011 through December 2018.
  • A total of 102 patients were included in the study, 72 with AML and 37 with MDS. Median age was 65 years old and median comorbidity index was 5. 56% of patients received a MRD transplant, and 97% received peripheral blood graft. Median mGFR was 81 mL/min/1.73m2.
  • When comparing pre-transplant mGFR vs. eCrCl, measured clearances were on average 12.3 mL/min/1.732 lower than calculated clearance, with a wide deviation in the differences between these (-65.3 to 40.7). 22 (20%) of patients had an mGFR < 65 mL/min/1.732, and 87 (80%) had an mGFR > 65 mL/min/1.732.
  • Median fludarabine and melphalan doses between the two groups were not significantly different, and only 13 patients received an empiric dose reduction in fludarabine (8), melphalan (4), or both (1). Overall NRM rate was 55% in the mGFR < 65 mL/min/1.732 group as compared to 31% in the mGFR > 65 mL/min/1.732 group (HR 2.13, P = 0.04). Neither eGFR < 65 mL/min/1.732 or eCrCl < 65 mL/min/1.732 predicted a difference in overall NRM between the two groups.
  • Patients with an mGFR < 65 mL/min/1.732 also experienced significantly higher rates of 100-day infections (HR 2.78, P < 0.001) and 1-year infections (HR 2.63, P < 0.001). No differences in relapse, engraftment, or GVHD were noted.
  • Authors conclude that mGFR may be favored over eCrCl or eGFR in the pre-transplant setting.

    Graft-versus-host disease
    *Kamada Y, Arima N, Hayashida M, et al. Prediction of the risk for graft versus host disease after allogeneic hematopoietic stem cell transplantation in patients treated with mogamulizumab. Leuk Lymphoma 2022;63(7):1701-1707. https://pubmed.ncbi.nlm.nih.gov/35225126/
    • Single-center, retrospective review looking at the characteristics of GVHD in patients post alloHCT for T cell leukemia/lymphoma who received mogamulizumab. Patient were excluded if they received a haploidentical HCT, a second alloHCT, had graft failure, or death due to ATL before engraftment
    • The cohort included 25 patients, 11 received mogamulizumab (Mog+) (6 before HCT, 5 after HCT due to disease recurrence) and 14 did not receive mogamulizumab (Mog–). The groups were similar in median age at diagnosis, conditioning regimens, graft sources, GVHD prophylaxis, and disease status at HCT
    • Cumulative incidence of grade II to IV GVHD in Mog+ was significantly higher than Mog– patients, especially among those who received mogamulizumab before HCT (p < 0.001)
  • Grade II to IV skin GVHD was observed in six Mog+ (54%) and two Mog– (14%) patients
  • Grade II to IV intestinal GVHD was observed in six Mog+ (54%) [5 mortalities related to GVHD or infection] vs. three Mog– (21%) patients [with no GVHD-related mortalities]
  • In patients treated with mogamulizumab after HCT, the median time to first dose was
  • 396.4 days (range 49-1672) and median number of doses before the onset of GVHD was

    2.5 (range 2-4). Two of the patients had grade IV GVHD

  • Mogamulizumab concentrations were measured in four Mog+ patients that received it prior to HCT and was found to be detectable for 4-5 months after last administration. The number of eTregs whose suppressive activity and CCR4 expression were higher than nTregs, which was persistently suppressed while mogamulizumab was detectable in serum, suggesting that mogamulizumab decreases Treg numbers for a period of time and may increase the risk of GVHD
  • The use of mogamulizumab before HCT in patients with ATL was a significant risk factor for developing severe GVHD, especially in the intestine. Although the study was small and retrospective in nature, the results suggest that serum concentration of mogamulizumab and eTreg numbers at the time of HCT could help predict the risk of developing GVHD in this patient population

    CAR-T cell therapy

    *Sehgal A, Hoda D, Riedell PA, et al. Lisocabtagene maraleucel as second-line therapy in adults with relapsed or refractory large B-cell lymphoma who were not intended for haematopoietic stem cell transplantation (PILOT): an open-label, phase 2 study. Lancet Oncol. 2022 Aug;23(8):1066-1077. doi: 10.1016/S1470-2045(22)00339-4. Epub 2022 Jul 12. https://pubmed.ncbi.nlm.nih.gov/35839786/

  • Open-label, phase 2 trial of lisocabtagene maraleucel (equal target CD8+ and CD4+ CAR+ T cells for a total target dose of 100 × 10⁶ CAR+ T cells) as second-line R/R LBCL therapy in 61 patients with at least one pre-specified TNI criteria: age ≥70 years, ECOG performance status ≥2, LVEF <50%, DLCO
  • ≤60%, CrCl <60 mL/min, or AST/ALT ≥2x ULN

  • A total of 61 patients received CAR-T, with the most common TNI criteria being age >70 years (51%) and ECOG score of 2 (26%). Overall response occurred in 49 (80% [95% CI 68–89]; p<0.0001) patients, including 33 (54% [41–67]) with CR. Median PFS was 9 months and median EFS was 7.2 months. At a median follow up of 17.6 months, median OS was not reached
  • The most common grade ≥ 3 ADRs were neutropenia (48%), leukopenia (21%), and thrombocytopenia (20%), with serious AEs related to lisocabtagene maraleucel reported in 13 (21%) patients. Cytokine release syndrome occurred in 23 (38%; grade 3 in one) patients and neurological events in 19 (31%; grade 3 in three) patients, with no grade 4 events or deaths and median one dose of tocilizumab (IQR 1–1). Eight (13%) of 61 patients had neurological events and were managed with corticosteroids only, with no steroid prophylaxis, and no grade ≥4 events. Grade ≥3 cytopenias not resolved by day 28 after infusion occurred in 18 (30%) of patients, with the majority recovering to grade 2 or better by day 90
  • Lisocabtagene maraleucel led to clinically significant and durable responses in a patient population with historically poor prognosis and no curative treatment options, supporting feasibility as second- line treatment in some patients who are not candidates for HCT due to age or performance status

    Supportive Care

    **Ohashi T, Aoki J, Ando T, et al. Clinical impact of cigarette smoking on the outcomes of allogeneic hematopoietic stem cell transplantation: a multicenter retrospective study. Bone Marrow Transplant. 2022;57(7):1124-1132. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3114301/

  • Multicenter study in adult patients at least 20 years of age who received alloHCT from 2010- 2015 was conducted to evaluate the correlation between smoking history, respiratory function and post-transplant outcomes.
  • 618 patients were included in the study and patients were divided into two groups classified according to the Brinkman index (BI) as non-smokers/light smokers (low BI) and heavy smokers (high BI).
  • The mean ages of the high and low-BI groups were 54 and 45 years, and 53% received myeloablative conditioning vs 68% for the high and low-BI groups, respectively. Patients were more likely to have high-risk disease in the high-BI group. Patients were otherwise similar with respect to performance status, hematopoietic cell transplant-comorbidity index, or stem cell source.
  • The high-BI group had a lower 5-year OS (52% vs. 39%, p = 0.01) and 5-year DFS (47% vs. 37%, p 0.03) than the low-BI group however after multivariate analysis, the rates were similar. There was no significant difference in 5-year relapse rate between groups.
  • The absolute 5-year incidence of cGVHD was significantly lower in the low-BI group than in the high BI group (49% and 57%, respectively, p < 0.01). However, there was no significant association between smoking and the incidence of cGVHD in the lungs (21% and 24%, respectively, p = 0.19) and between smoking and the incidence of bronchopneumonia (15% and 23%, respectively, p = 0.26).
  • Authors concluded that there was a significant association between cigarette smoking and cGVHD after alloHCT; therefore, post-transplant for these patients with a high BI management is important.

    *Saqr A, Carlson B, Staley C, et al. Reduced enterohepatic recirculation of mycophenolate and lower blood concentration after hematopoietic cell transplantation. Transplant Cell Ther 2022; 28: 372.e1- 372.e9. https://doi.org/10.1016/j.jtct.2022.04.018
    • Prospective, observational study to evaluate the association between the stool microbiome composition and abundance of mycophenolate enterohepatic recirculation (EHR) and the pharmacokinetics (PK) of mycophenolic acid (MPA) and its metabolites
    • Eligible participants were adults (18-75 years) with hematologic malignancies who underwent HLA-matched, haploidentical, or unrelated donor HCT after RIC or MAC. GVHD prophylaxis consisted of post-transplantation cyclophosphamide on days +3 and +4 followed by immunosuppression with MMF and tacrolimus starting on day +5. MMF was dosed at 1 gram IV every 8 hours over 2 hours. PK sampling was conducted on day +7 over one IV MMF dosing interval at steady state (a minimum of 3 unchanged doses)
    • PK analysis was conducted to provide concentration-time data of MPA, MPA glucuronide (MPAG), and acyl-glucuronide metabolite (acylMPAG) and analyzed by non-compartmental analysis. A second MPA peak, when present was observed at > 4 hours after the dose. The MPA

    EHR was defined as the ratio of MPA AUC4-8 to MPA AUC0-8 and was computed for each participant. Participants with MPA EHR above the median were considered to have high EHR, and those below the median were considered to have low EHR. Stool samples for DNA analysis were collected on the day of MMF PK sampling

  • Twenty HCT recipients (12 males, 8 females) were studied. The overall median MPA EHR was 22% with a median MPA EHR of 29% in the high EHR group and 12% in the low EHR group. The MPA troughs, MPA AUC4-8, and acylMPAG AUC4-8/AUC0-8 ratio was greater in the high EHR group than the low EHR group (1.53 µg/mL versus 0.28 µg/mL [p = .0001], 7.33 hour*µg/mL versus
  • 1.79 hour*µg/mL [p = .0003], and .33 hour*µg/mL versus .24 hour*µg/mL [p = .0007], respectively). MPA AUC0-8 was greater in the high EHR group than in the low EHR group with the difference trending toward significance (22.8 hour*µg/mL versus 15.3 hour*µg/mL; p= .06)

  • In the high EHR group, 80% of the subjects had MPA trough concentrations within the therapeutic range, compared with none in the low EHR group. Bacteroides vulgatus, Bacteroides stercoris, and Bacteroides thetaiotaomicron were 1.2 to 2.4-fold more abundant (p = .039, .024, and .046, respectively) in the high EHR group. MPA EHR was positively correlated with B.vulgatus and B.thetaiotaomicron and negatively correlated with Blautia hydrogenotrophica. There was more exposure to broad spectrum IV cephalosporins and/or vancomycin in the low EHR group versus the high EHR group in the 72 hours before pharmacokinetic sampling (80% versus 20%)
  • This study demonstrated that patients with high MPA EHR had greater abundance of Bacteroides species in stool and higher MPA exposure compared with patients with low MPA EHR. Bacteroides species likely produce β-glucuronidase which deconjugates MPAG in the intestine to MPA and is then readily enterohepatically recirculated. Through this activity Bacteroides species in the microbiome impacts MPA blood exposure and may positively impact immunosuppression but also may be related to MPA concentration-dependent toxicities. Larger studies may be helpful to corroborate these results and better define the acceptable bounds for optimal EHR

    **Khaled SK, Claes K, Goh YT, et al. Narsoplimab, a mannan-binding lectin-associated serine protease-2 inhibitor, for the treatment of adult hematopoietic stem-cell transplantation–associated thrombotic microangiopathy. J Clin Oncol. 2022 Aug 1;40(22):2447-2457. doi: 10.1200/JCO.21.02389. Epub 2022 Apr19. https://pubmed.ncbi.nlm.nih.gov/35439028/

    • Single-arm, open-label, phase II dose-escalation trial of narsoplimab, a fully human monoclonal antibody inhibitor of MASP-2 which serves as an effector enzyme for the lectin complement pathway and coagulation cascade activator. Patients received 4 mg/kg or flat 370 mg IV once weekly for 4-8 weeks for persistent alloHCT associated thrombotic microangiopathy (HCT-TMA), with 28 receiving at least one dose and analyzed for outcomes
    • Response, defined as improvement in platelets, lactate dehydrogenase and at least one organ function (kidney, pulmonary, gastrointestinal, or neurologic) occurred in 17 (61%) patients. Similar responses were observed across all patients by baseline features, HCT characteristics, and HCT complications subgroups. Improvement in organ function occurred in 74% of patients. Day 100 survival after HCT-TMA diagnosis was 68% and 94% in overall population and responders, respectively, with median OS of 274 days across all patients. Median time to response was 36 days (range 7 to 228 days)
    • Narsoplimab AEs were typical of the population, with most common treatment related ADRs being infection (61%), immune system disorders (18%), and respiratory/thoracic disorders (18%). No patients withdrew from the study due to AEs
    • Narsoplimab resulted in high response rates for HCT-TMA without apparent safety signals. No differences were observed in safety and efficacy between the two dosing regimens and similar responses were observed across all patient subgroups of the high-risk population

      **Ngo D, Samuels D, Chen J, et al. A Clinical Review of the Different Strategies to Minimize Hemorrhagic Cystitis Associated with the Use of Post-Transplantation Cyclophosphamide in an Allogeneic Transplant. Transplant Cell Ther. 2022 Jul; 28(7):349-354. https://pubmed.ncbi.nlm.nih.gov/35580733/
    • Incidence of hemorrhagic cystitis (HC) in haploHCT patients receiving PTCy is ~30% (range, 5.4% to 62%. Risk factors may include haploHCT, conditioning regimen, age, previous HCT and CMV reactivation
    • Prevention strategies include:
      • Hyper hydration: hydration at rates >200 ml/hr, however due to the risk of fluid overload in patients with comorbidities (CHF, ascites, etc.), alternative strategies such as mesna and continuous bladder irrigation (CBI) should be considered.
      • Mesna with/without hyper hydration: mesna doses of at least 100% of the PTCy dose should be given as either continuous infusion or frequent intermittent bolus infusion.
      • Antimicrobial use: ciprofloxacin prophylaxis in HCT patients for BKV has mixed data and should be used judiciously due to the risk for bacterial resistance. There is limited published data that describes a correlation between CMV and HC.
    • Currently, there is no consensus on optimal strategy to prevent PTCy-associated HC due to inconsistency with grading HC. Most HC studies are retrospective, and there are no studies comparing the prevention strategies
    • Authors concluded that more comparative studies between these strategies are needed to provide a definitive solution for preventing PTCy-associated HC

      **Marciano KA, Seago K, Dillaman M, et al. Evaluation of the Pharmacokinetic Interaction Between Letermovir and Tacrolimus in Allogeneic Hematopoietic Cell Transplantation Recipients. Transplant Cell Ther. 2022 Jul. 28(7):341.. https://pubmed.ncbi.nlm.nih.gov/35405369/
      • Retrospective review of adult alloHCT patients who received tacrolimus in combination with PO letermovir and had been receiving tacrolimus for at least 5 days before letermovir initiation at a single institution (n = 35)
        • Excluded patients who received strong CYP3A4 inhibitors (posaconazole, voriconazole) or IV tacrolimus
        • Variable timing of letermovir initiation but typically upon resolution of mucositis post HCT as long as tacrolimus trough concentration was not supratherapeutic at that time
        • Other medications that may have resulted in a weak or moderate PK interaction with letermovir and/or tacrolimus included fluconazole and dexamethasone (duration <7 days) in all patients, and one-time dose of (fos)aprepitant in 7 patients
      • Median percent increase in tacrolimus concentration-to-dose ratio over the 14-day period after initiation of letermovir was 22% on days 2 to 4, 47% on days 5 to 7, 66% on days 8 to 11, and 81% on days 12 to 14
    • Mean frequency of tacrolimus dose adjustments was 0.66 on days 2 to 4, 0.69 on days 5 to 7,
    • 1.06 on days 8 to 11, and 0.57 on days 12 to 14

    • Mean incidence of subtherapeutic tacrolimus trough concentrations was 9% and that of supratherapeutic tacrolimus trough concentrations was 32% during the 14-day evaluation period
    • Authors concluded that there is a substantial PK interaction between tacrolimus and letermovir, and close monitoring of tacrolimus trough concentration on initiation of letermovir should be considered


      AE: adverse events

      ICANS: immune effector cell-associated neurotoxicity syndrome

      alloHCT: allogeneic hematopoietic cell transplant

      MA: myeloablative

      aGVHD: acute graft versus host disease

      MASP-2: mannan-binding lectin-associated serine protease-2

      ALL: acute lymphoblastic leukemia

      MDS: myelodysplastic syndrome

      AML: acute myeloid leukemia

      MM: multiple myeloma

      ASCT: autologous stem cell

      MMF: mycophenolate mofetil

      AUC: area under the curve

      MMUD: mismatched unrelated donor

      BM: bone marrow

      MRD: minimal residual disease

      CART: chimeric antigen receptor T-cell

      MSD: matched sibling donor

      cGVHD: chronic graft versus host disease

      MTX: methotrexate

      CIBMTR: Center for International Blood and Marrow Transplant Research

      NMA: non-myeloablative

      CML: chronic myelogenous leukemia

      NRM: non-relapse mortality

      CNI: calcineurin inhibitor

      OS: overall survival

      CNS: central nervous system

      PBSC: peripheral blood stem cell

      CR: complete response

      PFS: progression-free survival

      CRS: cytokine release syndrome

      RFS: relapse-free survival

      DLCO: diffusing capacity of the lung for carbon monoxide

      RIC: reduced intensity conditioning

      ECOG: Eastern Cooperative Oncology Group

      TNI: transplantation not intended

      EFS: event free survival

      TMA: thrombotic microangiopathy

      GVHD: graft-versus-host disease

      URD: unrelated donor

      HCT: hematopoietic cell transplant


      HLA: human leukocyte antigen





      ASTCT Pharmacy SIG Research Working Committee:

      Arpita Gandhi, Jonathan Ptachcinski, Katie Gatwood, Andrew Lin, Jennifer Collins, Jitesh Kawedia, Dennis Marjoncu, Julianna Roddy, Lily Yan, Thomas Hughes, Sorana Ursu, Haval Norman

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