ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION for MULTIPLE MYELOMA Sep 29, 2018 Saurabh Chhabra, MD Assistant Professor of Medicine Division of Hematology/Oncology Medical College of Wisconsin, Milwaukee WI

Hematopoietic Stem Cell

Autologous vs. Allogeneic Transplant

Stem cell collection/harvest Allogeneic Hematopoietic Cell Transplantation = Stem Cell Transplantation = Bone Marrow Transplantation (BMT) Refers to the way (hematopoietic) stem cell are harvested/collected

Stem Cell Collection Patient Preparation Stem Cell Delivery

Allogeneic Transplant has been around for 5 decades Allogeneic Transplant is IMMUNOTHERAPY

Indications for Hematopoietic Cell Transplantation in the US in 2014 (CIBMTR)

Allogeneic Transplant: Who can be a donor? 1. “Matched” Sibling 2. “Matched” Unrelated Volunteer adult donor 3. Partially Mismatched (“Half-matched”) Sibling, Child or Parent

Probability of Finding a Matched Unrelated Donor Likelihood of Identifying a Matched Unrelated Donor (%) White European 75 African-Americans 16 Chinese 41 Hispanics 34 Gragert L. N Engl J Med. 2014;371(4):339-48

Allogeneic Transplant: How to select a donor? Matched Sibling Available? Yes No Matched Unrelated donor Available? Yes No Chemotherapy Haploidentical (“half-matched”) family donor available? Cord blood transplant Go To Transplant Yes Clinical Trial No

Allogeneic Transplant: Limitations Requires a donor Higher mortality (10-20%) Morbidity (rejection, infections, Graft-versus-Host Disease) Patients need long-term anti-rejection medications Theoretically curative: Risk of relapse is there! May still need treatment for Myeloma Expensive!

Trend in Allogeneic Transplants by Patient Age

Trends in Allogeneic Transplants by Patient Age The number of autologous and allogeneic transplants for treatment of malignant diseases in older patients continue to increase. Fourty-four percent of autologous transplant recipients and 22% of allogeneic transplant recipients in 2007-2013 were older than 60. *Transplants for AML, ALL, NHL, Hodgkin Disease, Multiple Myeloma

Staging Multiple Myeloma   5-Year survival Median survival R-ISS I 82% NR R-ISS II 62% 87 mon. R-ISS III 40% 56 mon.

High-Risk Multiple Myeloma: Definition

Clinical Trials of Allogeneic Transplant 1. Garban F et al. Blood. 2006 May 1;107(9):3474-80. 2. Bruno B et al. N Engl J Med. 2007 Mar 15;356(11):1110-20. 3. Rosinol Let al. Blood. 2008 Nov 1;112(9):3591-3. 4. Gahrton G et al. Blood. 2013 Jun 20;121(25):5055-63. 5. Krishnan A et al. Lancet Oncol. 2011 Dec;12(13):1195-203

Froedtert & Medical College of Wisconsin % Surviving Years after transplant Dhakal, B et al. Clinical Lymphoma, Myeloma & Leukemia, Vol. 16, No. 7, 379-86

Indications for allogeneic HCT Early relapse: <24 months after primary therapy or <18 months after autologous transplant. Tandem autologous – allogeneic transplant in high-risk myeloma patients. Discourage allogeneic transplant in patients with multiple relapses and truly refractory myeloma.

Froedtert & MCW Preference We offer allogeneic transplant to multiple myeloma patients to Those with early relapse (<24 months) after primary therapy that included autologous transplant OR Those who have high-risk MM (high-risk cytogenetics, plasma cell leukemia) AND Those who remain sensitive to therapy, and are able to achieve remission prior to transplant

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