Frequency of Molecular and PET/CT Complete Remissions in Patients with Multiple Myeloma after Autologous Followed by Reduced-Intensity Allogeneic Stem Cell Transplants.
Authors: Zhou Ping , Castro-Malaspina Hugo , Papadopoulos Esperanza B. , Young James W. , Miller Kenneth , Pandit-Taskar Neeta , Filippa Daniel A. , Fleisher Martin , Comenzo Raymond L. 
Published: October 2019

Despite recent advances multiple myeloma (MM) remains an incurable hemat</INS>ologic malignancy with a median survival of about 4 years. Autologous stem cell transplant (SCT) followed by reduced-intensity allogeneic SCT (tandem auto-allo) is a promising new approach designed to combine maximal tumor reduction and graft-versus-myeloma effect. The definition of complete response (CR) after tandem auto-allo is based on conventional serologic, radiologic, and pathologic parameters (Blade criteria). Because more sensitive molecular and radionuclear techniques are available, we evaluated the predictive value of these techniques after tandem auto-allo. Our hypothesis is that minimal residual disease (MRD) after tandem auto-allo likely predicts relapse and that, if identified early, patients with MRD may be candidates for novel salvage therapies. We employed patient-specific clonal Ig gene polymerase chain reactions using marrow and blood cells, and whole-body positron-emission tomography/CT scans (PET/CT) to assess patients after tandem auto-allo. PCR detects and estimates molecular MRD. PET/CT may detect occult medullary and extramedullary (soft tissue) disease. In patients achieving CR by the Blade criteria, we determined the frequency with which PCR and PET/CT findings were concordant. We have treated 10 patients with MM, 8 men and 2 women, with tandem auto-allo. Median age was 50.5 years (range, 37–58). There was no peri-transplant mortality, but 3 patients have died of progressive disease at 278, 398, and 402 days post-allo. Seven patients are alive at a median of 337 days (101–1187) post-allo, one with persistent myeloma and one awaiting evaluation. The remaining 5 patients are in CR by standard criteria (immunofixation negative). Their current status is shown below.

Age/Gender Status, days post-allo PCR (marrow) PET/CT 55M CR, d 1003 Neg on d 201, 924 Neg d 983 37W CR, d 632 Pos on d 452 Neg d 192 45M CR, d 337 Neg on d 88, 200 Equivocal d 222 39M CR, d 319 Pos on d 93, 177 Pos d 290 51M CR, d 172 Neg on d 104 Neg d 94

In sum, 2/5 have negative PCR and PET/CT findings; 1/5 has negative PCR and equivocal PET/CT findings; and 2/5 have positive PCR, one with positive PET/CT findings. Of note, all had negative PCR results using peripheral blood cells. The equivocal PET/CT showed low-level uptake in areas of prior myeloma in the pelvis. The positive PET/CT showed increased uptake in cervical and portacaval lymph nodes, but whether these findings represent occult myeloma is unclear. Overall, based on intention-to-treat in this small series, the frequency of CR with concordant PCR and PET findings is in the 20% to 30% range; and the frequency with which patients may become candidates for novel early salvage regimens is similar. A systematic approach using these methods after tandem auto-allo clearly merits further investigation.