Laura Cannon, PharmD MPH
PGY-2 Hematology/Oncology Pharmacy Resident
University of Colorado Skaggs School of Pharmacy
Aurora, CO

The 2019 Transplantation and Cellular Therapy (TCT) Meetings of the American Society for Blood and Marrow Transplantation (ASBMT) and the Center for International Blood and Marrow Transplant Research (CIBMTR), formerly known as the BMT Tandem Meetings, were held at the George R. Brown Convention Center in Houston, TX, February 20–24. This meeting welcomed physicians, clinical research professionals, pharmacists, and advanced practice providers for the purpose of discussing new and exciting issues in transplantation and cellular therapy.

During the meeting, a number of researchers were given best-abstract awards and oral presentation platforms in recognition of their work to advance the field of oncology. One of the best-abstract awards went to Peled and colleagues for their work on the evaluation of pretransplant microbiota injury and its effect on predicting overall survival. Their research showed a distinct difference between the gut microbiota of preallogeneic transplant patients compared to healthy individuals, establishing the pretransplant period as an important window of opportunity for evaluating microbiota injury, selecting conditioning regimens and prophylaxis, and implementing prevention strategies.¹ Sterner and colleagues received an award for their abstract, “GM-CSF Blockade during Chimeric Antigen Receptor T-Cell (CART) Therapy Reduces Cytokine Release Syndrome (CRS) and Neurotoxicity (NT) and May Enhance CART Effector Functions.” This abstract suggested that lenzilumab, an antibody that neutralizes granulocyte-macrophage colony-stimulating factor, may reduce both CRS and NT while enhancing CART function and warrants evaluation in a phase 2 clinical trial.²

Several oral presentations were given during the TCT meeting, including the “Long-Term Follow-Up of Tisagenlecleucel in Adult Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma: Updated Analysis of the Juliet Study,” by Schuster and colleagues. This study provided an updated overall response rate (ORR) of 54% (40% complete response [CR], 13% partial response [PR]; 95% confidence interval [CI]: 43%–64%), with a median 19-month follow-up. ORR was consistent across subgroup analysis based on receipt of prior autologous stem cell transplant and double- or triple-hit lymphoma.³

The TCT Pharmacists Conference was a 2-day event held February 22–23. Presentations focused on relevant issues and hot topics in the care of this patient population. In addition to pharmacists, the conference audience was made up of physicians, nurses, and advanced practice providers. Estimated conference attendance was 383, an increase from approximately 250 attendees in 2018.

To open the TCT Pharmacists Conference, Jason Yeh, clinical pharmacy specialist at the University of Texas MD Anderson Cancer Center, discussed the use of post-transplant cyclophosphamide (PTCy) for the prevention of graft-versus-host disease (GVHD) beyond haploidentical transplants. His presentation discussed the history of PTCy and focused on current use in therapy based upon the limited literature available and the differences in stem cell source.

In an update on infectious diseases, Erin McCreary, clinical pharmacist in antimicrobial stewardship and infectious diseases at the University of Pittsburgh Medical Center, presented on prevention and treatment strategies for cytomegalovirus (CMV). Her presentation gave an overview of CMV diagnostic challenges, reviewed preemptive therapy versus prophylaxis, and focused on the appropriate setting for the use of letermovir. Harrison Bachmeier, clinical pharmacist at Moffitt Cancer Center, presented “New Antimicrobials for Multidrug Resistant Organisms,” highlighting new antibiotic approvals and their appropriate use for the treatment of multidrug-resistant Pseudomonas and Acinetobacter and carbapenem-resistant Enterobacteriaceae.

Immunotherapy and targeted agents are changing our treatment of hematologic malignancies and reframing our treatment algorithms in the pre- and post-transplant setting. Katie Culos, clinical pharmacist at Vanderbilt University Medical Center, provided an overview of immune therapy in her presentation “Immune Therapy: Pre and Post Hematopoietic Cell Transplant,” by introducing different immune therapy agents, discussing their place in therapy for the treatment of various hematologic malignancies, and reviewing their use in the post-transplant setting for relapse prevention. Lydia Benitez, clinical pharmacy specialist at University of Michigan Medicine, presented “Evolving Treatment Options in Acute Myeloid Leukemia,” reviewing the recent approval of multiple agents that can be used as first-line treatment, either in the post-transplant setting or in the relapsed or refractory setting. In the setting of these new treatment options, she encouraged the audience to focus on oncology stewardship and specifically discussed clinical scenarios where the use of one agent over another may be preferred on the basis of clinical trial subgroup analysis results.

The TCT Pharmacists Conference included a best-abstracts session highlighting pharmacists’ research in a review of four exciting abstracts. The first, by Ashley Teusink-Cross, a clinical pharmacy specialist at Cincinnati Children’s Hospital, evaluated the safety and efficacy of ibrutinib for pediatric patients with chronic graft-versus-host disease (cGVHD). A total of 12 patients (ages 3–19) received ibrutinib 250 mg/m² (maximum 420 mg) daily. The majority of patients had severe cGHVD affecting the skin, lung, or eyes. Out of 12 patients, 8 patients remained eligible for evaluation at 6 months, with all 8 achieving a partial response and a reduced or discontinued steroid requirement. The most common adverse events identified were thrombocytopenia, neutropenia, and mouth sores.⁴

The second abstract, by Kathryn Maples, a bone marrow transplant clinical pharmacy specialist at Memorial Sloan Kettering Cancer Center, was a retrospective chart review assessing the need for empiric dose adjustments of calcineurin inhibitors (CNI) in 46 patients receiving letermovir post-transplant. The study showed an increase in CNI trough levels following the initiation of letermovir but concluded that the impact was not enough to warrant upfront CNI dose adjustment.⁵

Carmen Lau, a bone marrow transplant clinical pharmacy specialist at Memorial Sloan Kettering Cancer Center, continued the discussion of letermovir by reviewing her evaluation of the efficacy of letermovir prophylaxis in CMV seropositive cord-blood transplant patients compared to pre-letermovir controls. Her comparison showed that of 62 patients in the historical cohort receiving ganciclovir prophylaxis (days -7 to -2), 51 (82%) developed a CMV infection by day +100, compared to zero clinically significant CMV infections in the 10 patients receiving letermovir prophylaxis. Additionally, patients in the historical cohort who developed CMV infections had a high likelihood of experiencing renal or myelosuppressive toxicities associated with foscarnet, ganciclovir, or valganciclovir treatment; no toxicities were observed with letermovir.⁶

The final abstract, “Letermovir in Allogeneic Hematopoietic Cell Transplantation: Beyond the Label,” by Andrew Lin, a bone marrow transplant clinical pharmacy specialist at Memorial Sloan Kettering Cancer Center, assessed the efficacy of letermovir for primary or secondary prophylaxis in post-transplant patients. Of the 39 patients receiving letermovir as primary prophylaxis, two patients (5.1%) experienced a clinically significant CMV infection; no clinically significant CMV infections were observed in the 15 patients receiving letermovir as secondary prophylaxis.⁷

During the TCT meeting, voters approved changing the name of ASBMT to the American Society for Transplantation and Cellular Therapy (ASTCT), given the “increasing emphasis on new cell therapies.”

The next TCT meeting will be held February 19–23, 2020, in Orlando, FL. More information can be found at www.asbmt.org.

References

1. Peled JU, Gomes A, Stein-Thoeringer C, et al. Multicenter microbiota analysis indicates that pre-HCT microbiota injury is prevalent across geography and predicts poor overall survival. Biol Blood Marrow Transplant. 2019;25(3):S1.
2. Sterner RM, Sakemura R, Yang N, et al. GM-CSF blockade during chimeric antigen receptor T-cell (CART) therapy reduces cytokine release syndrome and neurotoxicity and may enhance CART effector functions. Biol Blood Marrow Transplant. 2019;25(3):S4.
3. Schuster SJ, Bishop MR, Tam CS, et al. Long-term follow-up of tisagenlecleucel in adult patients with relapsed or refractory diffuse large B-cell lymphoma: updated analysis of Juliet Study. Biol Blood Marrow Transplant. 2019;25(3):S20-S21.
4. Teusink-Cross A, Davies SM, Grimley MS, et al. Ibrutinib for the treatment of chronic graft versus host disease in pediatric patients. Biol Blood Marrow Transplant. 2019;25(3):S93-S94.
5. Maples KT, Maloy MA, Lin A, et al. Lack of a significant pharmacokinetic interaction between letermovir and calcineurin inhibitors in allogeneic HCT recipients. Biol Blood Marrow Transplant. 2019;25(3):S94.
6. Lau C, Politikos I, Maloy MA, et al. Letermovir prophylaxis demonstrates high efficacy in adult cytomegalovirus (CMV) seropositive cord blood transplant (CBT) recipients: a comparison with pre-letermovir era CBT controls. Biol Blood Marrow Transplant. 2019;25(3):S94-S95.
7. Lin A, Maloy MA, Bhatt V, et al. Letermovir in allogeneic hematopoietic cell transplantation: beyond the label. Biol Blood Marrow Transplant. 2019;25(3):S95-S96.