Bortezomib induction prior to autologous hematopoietic cell transplantation (AHCT) for newly diagnosed light chain amyloidosis (AL): A study of 426 patients.

Authors

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Robert F. Cornell

Vanderbilt University Medical Center, Nashville, TN

Robert F. Cornell , Parameswaran Hari , Stacey Goodman , Luciano J. Costa , Raphael Fraser , Noel Estrada-Merly , Shaji Kumar , Muzaffar H. Qazilbash , Anita D'Souza

Organizations

Vanderbilt University Medical Center, Nashville, TN, Medical College of Wisconsin, Milwaukee, WI, University of Alabama at Birmingham, Birmingham, AL, CIBMTR (Center for International Blood and Marrow Transplant Research), Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, CIBMTR (Center for International Blood and Marrow Transplant Research) Medical College of Wisconsin, Milwaukee, WI, Mayo Clinic, Rochester, MN, Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, Center for International Blood and Marrow Transplant Research/Medical College of Wisconsin, Milwaukee, WI

Research Funding

U.S. National Institutes of Health
U.S. National Institutes of Health

Background: AL is a clonal plasma cell (PC) disorder causing multiorgan dysfunction from amyloid fibril deposition. While bortezomib (B) induction has been used prior to AHCT recently, AHCT without prior induction has been a common practice. The primary objective of this study was to compare outcomes of AL patients who proceeded to AHCT without induction to those receiving pre-AHCT induction with B. Methods: Outcomes of 426 systemic AL AHCT recipients between 2014-2018 reported to the Center for International Blood and Marrow Transplant Research (CIBMTR) were reviewed. Patients receiving induction with therapy other than B, AHCT occurring > 9 months after diagnosis, no documented AL end-organ involvement, myeloma-defining events and conditioning other than melphalan (MEL) monotherapy were excluded. Multivariate analysis (MVA) was conducted to identify prognostic factors associated with relapse, PFS and overall survival (OS). Results: 286 patients received B induction therapy vs 140 patients receiving no induction. Age, gender, number and type of organs involved, and AL AHCT center volume were similar between the groups. Patients receiving induction had greater PC burden compared with no induction (PC ≥ 10%, 41% vs 11%, p < 0.01). Induction was B, cyclophosphamide and dexamethasone (D) in 83% followed by B, lenalidomide and D (10%) or B+D (7%). Median follow-up was 24.9 months. At 2 years, B induction vs. no induction was associated with 13% (95% CI 10-17%) vs 22% (95% CI 15-30%) relapse risk (p = 0.03); 83% (95% CI 79-87%) vs 74% (95% CI 66-81%) PFS (p = 0.04); 93% (95% CI 90-95%) vs 94% (95% CI 89-97%) OS (p = 0.7). On MVA, the B induction group had improved PFS (HR 0.46, 95% CI 0.3-0.7, p < 0.001) with similar OS (HR 0.6, 95% CI 0.3-1.2, p = 0.1) compared with no induction. Creatinine < 2 mg/dl (HR 0.55, 95% CI 0.3-0.9, p = 0.02) and Karnofsky score ≥90 (HR 0.51, 95% CI 0.33-0.78, p < 0.01) were also associated with improved PFS. MEL dose < 180 mg/m2 was associated with inferior PFS (HR 2.17, 95% CI 1.31-3.61, p < 0.01) and OS (HR 3.6, 95% CI 1.5-8.6, p < 0.01). No deaths were seen in the first 100 days post-AHCT. At last follow-up, 32 deaths occurred, 26 (81%) due to AL. Conclusions: Compared with prior CIBMTR analyses, B induction use has increased in AL AHCT recipients and a higher PC burden was the only clinical determinant. Furthermore, B induction was associated with lower relapse and improved PFS at 2 years with no OS difference despite higher proportion of patients with > 10% PC, which has been associated with poor outcomes.

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Abstract Details

Meeting

2020 ASCO Virtual Scientific Program

Session Type

Poster Discussion Session

Session Title

Hematologic Malignancies—Plasma Cell Dyscrasia

Track

Hematologic Malignancies

Sub Track

Cell Therapy, Bispecific Antibodies, and Autologous Stem Cell Transplantation for Plasma Cell Disorders

Citation

J Clin Oncol 38: 2020 (suppl; abstr 8515)

DOI

10.1200/JCO.2020.38.15_suppl.8515

Abstract #

8515

Poster Bd #

415

Abstract Disclosures