Clofarabine with topotecan, vinorelbine, and thiotepa reinduction regimen for children and young adults with relapsed AML

Effective reinduction regimens are needed for children with relapsed and refractory acute myeloid leukemia (AML) as outcomes remain poor. Therapeutic options are limited in this heavily pre-treated patient population, many of whom have reached lifetime recommended doses of anthracycline chemotherapy. The development of effective non-anthracycline based salvage regimens is crucial to these patients who are at significant risk of life-threatening cardiotoxicity. We previously reported results of a phase 2 trial of a clofarabine-based regimen with topotecan, vinorelbine, and thiotepa (TVTC) in patients with relapsed acute leukemias. Here we report on an expanded bicenter cohort of 33 patients, <25 years of age, with relapsed/refractory (R/R) AML treated with up to 2 cycles of the TVTC reinduction regimen from 2007 to 2018. The overall response rate (ORR), defined as complete remission (CR) or CR with partial recovery of platelet count (CRp), was 71.4% (95%CI: 41.9 to 91.6%) for those patients in first relapse (n=14) and 47.4% ( 95%CI: 24.4 to 71.1%) for patients in 2nd or greater relapse or refractory disease. Responses were seen across multiple high risk cytogenetic and molecular subtypes, with 84% of responders successfully bridged to allogeneic stem cell transplantation. The 5-year OS for patients in first relapse was 46.2% (95%CI: 19.1 to 73.3%) and 50.0% (95%CI: 26.9 to 73.1%) for patients who responded to TVTC. For pediatric and young adult patients with R/R AML, TVTC reinduction compares favorably with currently used salvage regimens and warrants further exploration.

Venetoclax in Relapsed/Refractory Acute Myeloid Leukemia: Are Supporting Evidences Enough?

Despite the progress in the development of new therapeutic strategies, relapsed/refractory (R/R) acute myeloid leukemia (AML) still represents a high unmet medical need. Treatment options in this setting include enrollment into clinical trials, allogeneic stem cell transplantation and/or targeted therapy. Nevertheless, it is associated with poor outcomes. Thus, the development of new treatments, which could ameliorate the prognosis of these patients with a good safety profile are highly demanded. Recently, venetoclax (VEN) has been approved for naïve AML patients unfit for intensive chemotherapy. In this regard, regimens including VEN could represent a valuable treatment option even in those with R/R disease and several studies have been conducted to demonstrate its role in this clinical setting. This review aims to summarize the current evidence on the use of VEN regimens in the treatment of R/R AML.

First Salvage Therapy for Relapsed or Refractory Acute Myeloid Leukemia: Associated Health Care Resource Use and Costs

Background For relapsed/refractory acute myeloid leukemia (R/R AML), treatments used include high-intensity cytotoxic chemotherapy regimens (HIC); low-intensity chemotherapy (LIC); targeted therapies administered as either a single agent or as part of combination therapy; or venetoclax, often in combination with LIC. As options increase for patients with R/R AML, an understanding of the real-world health care resource use (HRU) and costs associated with different treatment regimens is needed. Objective We described HRU and costs associated with HIC alone, LIC alone, and select novel, orally administered therapies (alone or in combination with chemotherapy) to better understand HRU and costs of first salvage therapy for AML. Methods This was a retrospective analysis using the IBM MarketScan ® database which contains medical and drug data from ~40 million people annually who are covered by employer-sponsored private health insurance in the United States. The time frame for this claims analysis was 1/1/2017-12/31/2019. HRU and costs were estimated for 5 mutually exclusive treatment groups: HIC alone, LIC alone, gilteritinib, other FLT3 tyrosine kinase inhibitors (TKIs), and venetoclax. Gilteritinib, other FLT3 TKIs, and venetoclax treatments could be single-agent or in combination with chemotherapy. Patients aged ≥18 years at AML diagnosis with continuous health plan enrollment for ≥180 days prior to first AML diagnosis and through start of first salvage therapy were included in the analysis. Evidence of R/R AML was determined by diagnosis code and use of a treatment-based algorithm (Grinblatt DL, et al. Blood. 2020;136[Suppl. 1]:24-25). Descriptive statistics were used to characterize baseline patient demographic and clinical characteristics and HRU and costs through treatment. HRU and costs were reported as per-patient per-month (PPPM). Results Most baseline characteristics were similar across treatment groups (eg, % male, 45.6%-57.1%; mean Charlson comorbidity scores, 3.07-3.86; and mean all-cause health care costs during 6-months pretreatment, $201,583-$253,437). Mean (SD) patient age overall was 54.1 (14.9) years; the venetoclax group appeared older (61.2 years). The frequency of prior HIC treatment in the overall sample was 38.1%; a majority of patients treated with gilteritinib (64.3%) and other FLT-3 TKIs (55.9%) had prior HIC treatment. Of patients receiving gilteritinib, other FLT3 TKIs, and venetoclax, 6 (42.9%), 33 (48.5%), and 77 (96.3%) respectively, were receiving concomitant chemotherapy. Almost all patients were hospitalized during HIC; the percentage of patients requiring hospitalization was lower and comparable across other treatment groups (Table). Hospital length of stay was highest in the HIC group and lowest in the gilteritinib group. Intensive care unit stays PPPM were highest in the HIC and venetoclax groups and lowest in the gilteritinib group. In the outpatient setting, physician office visits and outpatient hospital visits PPPM were higher in the LIC, other FLT3 TKIs, and venetoclax groups and lower in the HIC and gilteritinib groups (Table). Transfusion-related physician office and outpatient hospital visits PPPM were higher in the venetoclax group than in the other groups. The highest health care costs PPPM were in the HIC group with costs being similar for the other treatment groups (Table). Inpatient costs were highest in the HIC group and lowest in the gilteritinib group; outpatient costs were highest in the LIC and venetoclax groups and lowest in the HIC, gilteritinib, and other FLT3 TKI groups. Transfusion costs in the outpatient setting were the highest in the venetoclax group and the lowest in the gilteritinib group. Prescription claim costs were the highest in the gilteritinib group and lower in the HIC, LIC, and venetoclax groups. Conclusion Across select treatments for R/R AML in first salvage, inpatient HRU was generally the highest for the HIC group while outpatient HRU was generally the highest in the LIC and venetoclax groups, with the highest number of outpatient transfusion visits noted in the venetoclax group. Analyses of total all-cause costs showed that costs were the highest in the HIC group and similar in the LIC, gilteritinib, other FLT3 TKIs, and venetoclax groups. Although prescription drug costs were high in the gilteritinib group, these high costs were partially offset by low HRU in both the inpatient and outpatient settings. Figure 1 Figure 1. Disclosures Muffly: Adaptive: Honoraria, Other: fees for non-CME/CE services: , Research Funding; Astellas, Jasper, Adaptive, Baxalta: Research Funding; Pfizer, Amgen, Jazz, Medexus, Pfizer: Consultancy. Young: Astellas Pharma, Inc.: Current Employment. Nimke: Astellas Pharma, Inc.: Current Employment. Sullivan: Astellas Pharma, Inc.: Current Employment. Feng: Astellas Pharma, Inc.: Current Employment. Pandya: Astellas Pharma, Inc.: Current Employment.

Implementation of Inpatient Palliative Care Consultation Triggers and Its Impact on Healthcare Use in Patients with Relapsed/Refractory Acute Myeloid Leukemia

Background: Patients with relapsed/refractory acute myeloid leukemia (AML) have poor outcomes and high levels of healthcare utilization at end of life. Palliative care remains underused in this population despite the high symptom burden. Questions remain regarding how best to integrate palliative care for high risk hematology patients. Prior implementation of standardized palliative care consultation triggers on an inpatient solid tumor service led to increased palliative care consultations and decreased healthcare utilization (Adelson et al, JOP 2017). We conducted a prospective cohort study evaluating standardized palliative care consultation triggers for patients admitted to a tertiary academic center with advanced AML. Method: Trigger criteria were developed for hospitalized patients with hematologic malignancies on the inpatient hematology floors at Smilow Cancer Hospital and included: 1) persistent disease after ≥ 2 lines of therapy, 2) length of stay (LOS) >7 days for symptom management, 3) Eastern Cooperative Oncology Group (ECOG) performance status > 2, and 4) refractory graft versus host disease (GVHD) after ≥ 3 lines of therapy. Patients with relapsed/refractory AML were included if they met criteria #1. A palliative care nurse coordinator performed chart review of admitted patients 1-2 times per week from June to December 2020 and contacted the primary team when a patient met eligibility. Patient characteristics and healthcare outcomes were compared with patients with AML meeting criteria #1 admitted pre-intervention (June to December 2019) using Fisher t-tests. Results: A total of 110 admitted patients with advanced AML met eligibility criteria #1 (64 pre-intervention and 46 post-intervention). Baseline patient and disease characteristics were similar, including mean age at admission (60.4 vs 60.9 years, p=0.848), gender (64% vs 59% male, p=0.691), prior transplant (56% vs 52%, p=0.702), and AML risk stratification (67% vs 78% adverse risk, p=0.283). In the post-intervention group, 61% of eligible patients were screened. Of the screened patients, 54% received a palliative care consult, 18% were declined by the primary team, 14% were marked as not eligible, and 14% did not have a palliative care consult with reason unspecified. Within the same admission, there was a significant increase in advance care planning and/or advanced directive documentation post-intervention (13% vs 28%, p=0.049). There was no differences in pre- and post-intervention groups in time to palliative care consult from admission (7.2 vs 4.9 days, p=0.245), LOS (12.13 vs 12.33 days, p=0.941), 30-day readmissions (52% vs 39%, p=0.246), critical/intermediate care escalation (22% vs 13%, p=0.318) during the same admission. By July 2021, 92% of the pre-intervention patients and 57% of the post-intervention patients were deceased. Of the deceased patients, there was no differences in pre- and post-intervention groups in blood transfusions (100% vs 96%, p=0.306) or hospice enrollment (46% vs 62%, p=0.157) within 14 days of death. There was also no significant differences in pre- and post-intervention groups in non-palliative anti-neoplastic therapy use (37% vs 38%, p=0.999), hospital admissions (95% vs 88% p=0.364), or critical/intermediate care escalation (51% vs 38%, p=0.350) within 30 days of death. Conclusion: A trigger-based palliative care referral intervention is feasible and doubled palliative care use in patients with relapsed/refractory AML. Our intervention was associated with increased advance care planning documentation during the admission. There were directional changes in other healthcare measures, including decreased time to palliative care consult and escalation of care, as well as increased hospice enrollment. These differences, however, were not statistically significant due to the small sample size. The significant healthcare use likely reflected high symptom burden at end of life, associated with transfusions and admissions for infection and symptom management. More research is needed to determine how best to support these patients at end of life. Of note, our intervention period occurred during the COVID-19 pandemic, which may have impacted threshold for inpatient admissions and the inpatient census. Disclosures Adelson: Carrum Health: Other: Stock; Abbvie: Consultancy; Roche/Genentech: Consultancy, Honoraria, Patents & Royalties, Research Funding; Heron: Consultancy; Celgene: Consultancy. Prebet: BMS: Research Funding; BMS, Curios, Daichi: Consultancy.

Venetoclax, Actinomycin D and Low Dose Cytarabine for Relapsed or Refractory Acute Myeloid Leukemia in Clinical Practice Setting

Background Venetoclax based therapies have produced varying results in the relapsed or refractory acute myeloid leukemia (R/R AML) setting. Highest response rates were demonstrated after Venetoclax in combination with high dose chemotherapy. However, this approach is feasible mainly in fit, younger patients. Herein, we present a lower intensity combination therapy consisting of Venetoclax, low dose Cytarabine and Actinomycin D (ACTIVE) in patients with R/R AML administered in real-life clinical practice setting. Methods We performed an observational, retrospective, single centre study. The patients were at least 18 years of age and had R/R AML. All patients provided informed consent for treatment as well as data collection. Venetoclax ramp-up was administered over either 3 or 5 days until the daily dose of 600mg/d was reached. The ACTIVE regimen consisted of Venetoclax 600mg/d p/o on days 1-28, Cytarabine 20mg/m 2 s/c on days 1-10, Actinomycin D 12.5 µg/kg i/v on days 1, 2 and 3 (on days 1 and 2 for patients ≥65 years). Strong/moderate CYP3A inhibitors/inducers or Venetoclax dose reductions were not allowed. Indications for stopping Venetoclax before Day 28 were life threatening infectious complications or faster hematological recovery with the addition of G-CSF in responders. A second ACTIVE cycle was administered in non-responders without evidence of progressive disease after Cycle 1 or in responders with positive minimal residual disease (MRD). We evaluated baseline characteristics, composite CR (CRc = CR + CRi + CRp), overall response (ORR = CRc + MLFS), MRD negativity rates, overall survival (OS), relapse-free survival (RFS), event-free survival (EFS), Grade 3-5 non-hematological toxicities and Day 30 and Day 60 mortality rates. Results Fifty R/R AML patients were treated with ACTIVE and 56% (28/50) were male. The median age was 65 years (20-84). The median Eastern Cooperative Oncology Group (ECOG) status was 1 (0-3) and 40% (20/50) had ECOG status of 2 or 3. Secondary AML was confirmed in 48% (24/50) of cases. Adverse cytogenetics were identified in 28% (14/50) of patients whereas 60% (30/50) were stratified to adverse risk group in accordance with ELN 2017 guidelines. The most common gene mutations were IDH1/2 30% (15/50), FLT3 28% (14/50), ASXL1 22% (11/50), NPM1 14% (7/50), N/KRAS 12% (6/50) and RUNX1 12% (6/50). The median number of prior therapies was 2 (1-5). Intensive chemotherapy was administered in 80% (40/50) of whom 38% (15/40) had primary refractory disease and 48% (19/40) had previously received Fludarabine + Cytarabine + Idarubicin (FLAG-Ida) or Cytarabine + Mitoxantrone (HAM). Eight percent (4/50) had had prior Venetoclax exposure. Thirty-six percent (18/50) had relapsed after allogeneic stem cell transplantation (alloSCT) with a median time of 7.4 months (1.6-37.3) from transplant to relapse. One cycle of ACTIVE therapy was administered in 76% (38/50) of cases, whereas 24% (12/50) received 2 cycles. The median number of Venetoclax 600mg/d days per cycle was 18 (8-28). Additional FLT3/RAS/BCR-ABL1 inhibitors Gilteritinib, Trametinib or Dasatinib were administered in 12% (6/50). Forty-nine patients were evaluable for response and one patient died of sepsis before response evaluation (Table 1). The ORR was 73% (36/49) and the CRc rate was 67% (31/46). MRD negativity was confirmed in 61% (19/31) of CRc patients. Sixteen patients had undergone additional early bone marrow evaluations. Blast count reduction to <5% was observed in 50% (8/16) after Venetoclax ramp-up and in 88% (14/16) on Day 4. Half of the ACTIVE responders (18/36) continued maintenance therapy with Venetoclax + low dose Cytarabine and optional DLI, whereas 36% (13/36) proceeded to either first or second alloSCT. After 16.4 months of median follow-up, the median OS, RFS and EFS were 13.1, 7.2 and 4.5 months, respectively (Figure 1A). Median OS was not reached in MRD negative patients (Figure 1B). In multivariable Cox regression analysis, adverse cytogenetics (HR 3.48, 95% CI 1.39 -8.55) and primary refractory disease (HR 2.54, 95% CI 1.05-6.12) were associated with worse OS. The most common grade 3-5 non-hematological adverse events were febrile neutropenia (54%, 27/50) and bacteremia/sepsis (34%, 17/50). Day 30 and Day 60 mortality rates were 8% (4/50) and 16% (8/50), respectively. Conclusions ACTIVE was effective and well tolerated in this unselected prognostically unfavourable older R/R AML patient population. Figure 1 Figure 1. Disclosures Zucenka: Jannsen: Honoraria, Other: Travel-expenses; Takeda: Other: Travel Expenses; Novartis: Honoraria, Other: Travel Expenses; Pfizer: Honoraria, Other: Travel Expenses; Astellas: Honoraria; Abbvie: Honoraria, Other: Travel Expenses. Maneikis: Abbvie: Honoraria. Pileckytė: Abbvie: Honoraria, Other: Travel Expenses. Griškevičius: Abbvie: Other: Travel Expenses. OffLabel Disclosure: Venetoclax has been used off-label for the treatment of R/R AML

Venetoclax Therapy in a Heavily Treated Cohort of Patients with Relapsed or Refractory Acute Myeloid Leukemia: Update of the Pethema Registry Experience

Introduction The prognosis of patients with relapsed or refractory acute myeloid leukemia (RR-AML) is very poor, and treatment options are very limited. The exciting results of venetoclax (VEN) in untreated AML have led to its off-label use in RR-AML. However, evidence in RR-AML is still scarce and the available data are mostly from retrospective and single-center studies. The aim of our study was to analyze the effectiveness of VEN use in patients with RR-AML reported to the PETHEMA AML epidemiological registry. Initial results were presented previously (Labrador J, et al. ASH 2020). Here, we report an updated analysis. Methods We conducted a retrospective, multicenter, observational study of a cohort of patients with AML-RR who were treated with venetoclax in the hospitals of the PETHEMA group. We evaluated efficacy, CR/CRi rate and overall survival (OS). We performed a descriptive analysis. Overall survival (OS) was calculated using the Kaplan-Meier method. Results Fifty-one patients were included, 33 men and 18 women, with a median age of 68 years (25-82). The main characteristics of the included patients are shown in Table 1. With a median follow-up of 167 days, 10/51 patients (19%) continued to receive VEN at the time of analyses. Patients received a median of 2 cycles (0-8). VEN was administered with azacitidine (AZA) in 59%, with decitabine (DEC) in 29% and with low-dose cytarabine (LDAC) in 12% of patients, respectively. The CR/CRi and partial response (PR) rates were 12.4% and 10.4%, respectively. The CR/RCi and overall response (ORR, CR/CRi+PR) was higher in patients receiving VEN+AZA (17.9% and 32.1%) than in those receiving DEC + VEN (6.7% and 13.3%) or LDAC + VEN (0%). The presence of NPM1 or CEBPA variants were the only two variables associated with increased CR/CRi with VEN in RR-AML. Median OS was 104 days (95% CI: 56 - 151) (Figure 1A), 120 days in combination with AZA, 104 days with DEC, and 69 days with LDAC; p=0.875. Treatment response (Figure 1B) and ECOG 0 were the only variables that influenced OS in a multivariate model adjusted for age and sex (Table 2). VEN-resistant patients who received subsequent salvage therapy had superior median OS (98 vs. 5 days, p=0.004).Twenty-eight percent of patients required discontinuation of VEN due to toxicity. Sixty-one percent of patients required admission, mainly due to infections (45%), 10% due to bleeding and other causes in 12%. One case of tumor lysis syndrome was described. Conclusions Our real-life series depicts a marginal probability of CR/CRi and poor OS after venetoclax-based salvage. Patients treated with this regimen had very poor-risk features, and were heavily pre-treated, which could explain in part the observed poor outcomes. Although follow-up is still short, the small proportion of responders did not reach the median OS. Further studies will help to identify those patients potentially benefiting from venetoclax-based salvage regimens. Figure 1 Figure 1. Disclosures Belén Vidriales: Roche: Consultancy; Novartis: Speakers Bureau; Astellas: Consultancy, Speakers Bureau; Jazz: Consultancy, Speakers Bureau. Pérez-Encinas: Janssen: Consultancy. Tormo: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Jazz Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Astellas: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Montesinos: Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Glycomimetics: Consultancy; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Karyopharm: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Daiichi Sankyo: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Forma Therapeutics: Consultancy; Sanofi: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Teva: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Stemline/Menarini: Consultancy; Tolero Pharmaceutical: Consultancy; Agios: Consultancy; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Astellas Pharma, Inc.: Consultancy, Honoraria, Other: Advisory board, Research Funding, Speakers Bureau. OffLabel Disclosure: Venetoclax for Patients with Relapsed or Refractory Acute Myeloid Leukemia

Haploidentical Natural Killer Cell Therapy As an Adjunct to Stem Cell Transplantation for Refractory Acute Myeloid Leukemia

Refractory acute myeloid leukemia (AML), defined as failure of 2 cycles of induction therapy at diagnosis or of 1 cycle at relapse, represents a subgroup with poor clinical outcomes. In our transplant cohort, the 5-year overall survival in this subgroup was 16% (Ganapule at al. JGO 2017). Haploidentical natural killer cell (NK) therapy is a strategy that is being explored in refractory malignancies. Our in-vitro and animal model data suggest that exposure to arsenic trioxide (ATO) results in enhanced NK cytotoxicity (Alex AA et al. Front. Immunol 2018). Historically, at our center, patients with refractory AML have been treated with cytoreductive therapy (FLAG ± idarubicin or mitoxantrone + etoposide for 3 to 5 days) followed by 1-week rest and then a reduced-intensity transplant with fludarabine + melphalan conditioning while in peak cytopenia. From February 2019, we initiated a phase II single arm clinical trial (CTRI/2019/02/017505) enrolling patients with refractory AML planned for a stem cell transplant in peak cytopenia. Patients received CD56-positive cells from an HLA haploidentical related family donor (other than the stem cell donor, wherever feasible) following cytoreductive chemotherapy. The NK cell donor preference strategy included presence of KIR ligand mismatch, greater number of KIR B motifs (or the B score), lower donor age, and negative donor specific antibodies tested using flowcytometry crossmatch (Figure 1a). CD56-positive selection was done using CliniMACS prodigy system. This was followed by overnight incubation of the CD56 positive cells in autologous plasma with 2 micromolar ATO and 500 U/mL of interleukin-2. The CD56 positive cells were then infused to the patient 1-day after the completion of cytoreductive chemotherapy. This was followed by a reduced intensity stem cell transplant (Figure 1b). The primary outcome variable was 1-year relapse free survival. From February 2019, 14 patients with median age 28 years (IQR: 15.75-31.5) were enrolled in this trial. Six were females. Six had primary-refractory AML while 8 had relapsed-refractory AML. The cytoreductive chemotherapy was FLAG ± idarubicin (n=7), Mitoxantrone + Etoposide (n=6) and GCLAC (n=1). The median blast percentage on flowcytometry MRD testing prior to NK infusion was 15.9% (IQR: 9.1%-54.5%) (n=11). The median B score for the NK cell donors was 2 (IQR: 1-3). The median age of the NK cell donor was 43 years (IQR: 36-49.5). KIR ligand mismatch with the patient was noted in 2 donors. The median CD56-cell dose infused was 46.16 x 10 6/kg (IQR: 25.06-70.36) (Figure 1c). Pre-defined release criteria, including sterile cultures, and endotoxin negativity were met in all cases. There was no infusion related toxicity. The median blast percentage on flowcytometry MRD testing done following NK cell infusion was 11.9% (IQR: 4.9%-47.6%) (n=8). One patient withdrew consent after NK cell infusion and did not undergo transplant. For the remaining 13 patients, the stem cell donor was HLA matched (n=4), HLA 9/10 matched (n=1) or HLA haplomatched (n=8). The median CD34 cell dose infused was 10 x 10 6/kg (IQR:7.51-11.6). Five (38.5%) patients died of immediate post-transplant complications (sepsis (n=3) on days 1, 2 and 28, cerebral venous sinus thrombosis (n=1) on day 1 in a patient treated with hormonal contraceptives for menorrhagia, and veno-occlusive disease (n=1) on day 15 in a patient undergoing a second transplant) while 2 (15.4%) did not engraft (both subsequently died of infective complications following engraftment post-second transplant). Of the remaining 6 (46.2%) patients who engrafted and survived beyond 1 month of the transplant, the day 28 post-transplant MRD was negative for 5 patients while it was positive in 1 patient (0.13%). On follow up, 2 (15.4%) patients developed disease relapse (on days 54 and 218 respectively) and died. The remaining 4 (30.8%) patients are alive and relapse free at last follow up (mean follow up of surviving patients is 16 months). One patient received a CD34 cell boost on day 96 (cell dose - 8.55 x 10 6/kg) for poor graft function. For the entire cohort, the estimated 1-year event free survival is 28.8% ± 13.1%(Figure 1d). Whereas, acute GVHD was noted in 3 patients (50%; out of 6 evaluable patients) and chronic GVHD was noted in 3 patients (50%; out of the 6 evaluable patients). Thus, haploidentical NK cell therapy as an adjunct to transplant is safe and merits further evaluation in patients with AML. Figure 1 Figure 1. Disclosures Mathews: Christian Medical College: Patents & Royalties: US 2020/0345770 A1 - Pub.Date Nov.5, 2020; AML: Other: Co-Inventor.