Pretransplant PET Positivity Predicts Early Relapse with Poor Outcome in Patients of Multiple Myeloma Undergoing Autologous Stem Cell Transplantation

Background:

Multiple Myeloma is a heterogeneous disease with few patients enjoying overall survival up to a decade while others dying within few years from diagnosis. Multiple staging systems and risk stratification models based on clinical features, laboratory parameters and cytogenetics have been used to predict the response to therapy and outcomes. Positron emission tomography integrated with computerised tomography (PET-CT) offers several advantages as compared to conventional bone imaging modalities in terms of ability to assess extramedulary disease, detection of bone marrow involvement and extent of active disease. Especially important is ability of PET-CT to assess treatment response in terms of FDG activity as bone changes like lytic lesions may persist long on conventional imaging even when disease is in remission. There is scarce data on potential role of PET-CT in response evaluation and prognostication in patients with multiple myeloma. We prospectively analysed the prognostic relevance of PET-CT done prior to autologous stem cell transplant (ASCT).

Method:

Consecutive patients of multiple myeloma who underwent ASCT between March 2011 and June 2014 were included in this study. All patients received standard novel agent based induction regimen, bortezomib based in 38 patients and lenalidomide based in 5 patients. Patients were evaluated for response by using international myeloma working group (IMWG) criteria after 4-6 cycles of induction regimen. Subsequently patient's stem cells were harvested from peripheral blood by chemomobilization with cyclophosphamide along with G-CSF. All patients underwent PET-CT immediately pretransplant along with response evaluation by IMWG criteria. PET-CT was considered to be negative if there were no FDG avid lytic lesion and no FDG avid extramedulary disease/soft tissue component was seen. Conditioning regimen used for ASCT were melphalan- 200mg/m² in 37 patients, reduced doses of melphalan (100-140 mg/m²) in 2 patients or bortezomib- melphalan in 4 patients. Post transplant response evaluation was done at 3 months from transplant and at 3 monthly interval thereafter by SIEP, immunofixation, 24 hours urine BJP, and serum free light chain assay. Probabilities of overall survival and progression free survival were estimated using the Kaplan–Meier method and were compared by log rank test.

Results:

Forty three patients of multiple myeloma underwent ASCT during the study period. The median age of patients at diagnosis was 49 years and 31 (72 %) were male. As per International Staging System, 15 were stage I, 9 were stage II and 14 were stage III disease at time of diagnosis. After induction therapy, 17 patients achieved CR, 13 patients achieved VGPR, 10 patients had PR while 3 patients had progressive disease (PD) pretransplant. Simultaneously done PET-CT was positive in 15 (34%) patients while it was negative in remaining. At a median follow up of 2.6 years from diagnosis 8 patients had progression of disease and 3 patients have died because of disease progression. So as to evaluate the prognostic utility of PET-CT, patients were grouped into four groups as follows- group 1 - CR/VGPR and PET-CT- negative, group 2 - CR/VGPR and PET-CT- positive, group 3 - PR/PD and PET-CT- negative, group 4 - PR/PD and PET-CT- positive as shown in table 1.

At a median follow up of 1.68 years post transplant, 4 patients from group 1 and 4 patients from group 4 have progressed. The estimated probability of overall survival and progression free survival from transplant by Kaplan–Meier method at 3 year is 92 % and 62 % respectively. The time to progression after transplant was significantly short in group 4 as compared to group 1 (median time to progression of 6 months versus 26 months; p=0.001). Out of 8 patients who have relapsed post transplant, 3 patients who were PET-CT positive pretransplant have died while all the 4 patients who were PET negative pretransplant are alive.

Conclusion:

Pretransplant PET-CT positivity predicts early relapse after ASCT. Survival of such patients is poor after relapse post ASCT. These findings needs validation in larger cohort of patients with longer follow up.