Contributions
Abstract: EP1259
Type: E-Poster Presentation
Session title: Stem cell transplantation - Clinical
Background
Autologous stem cell transplant (ASCT) remains standard of care for eligible newly diagnosed myeloma patients (TE NDMM). Induction prior to ASCT frequently includes lenalidomide, reported to have an adverse effect on peripheal blood stem cell (PBSC) harvest in some studies.
Aims
The UK NCRI Myeloma XI/+ study compared induction combinations including thalidomide or lenalidomide giving the opportunity to compare PBSC harvests between patients treated with different immunomodulatory agents.
Methods
TE NDMM patients were randomised to triplet combinations, thalidomide or lenalidomide plus dexamethasone and cyclophosphamide (Tdc/Rdc) or the quadruplet combination carfilzomib+Rdc (KRdc). Induction was given for a min. of 4 cycles but continued to max. response. Patients who received Tdc/Rdc and achieved a max. response less than VGPR underwent response-adapted intensification therapy.
PBSC harvest was planned to occur after the completion of induction+/-intensification. Stem cell mobilisation and harvest was performed according to local practice with advice to aim for the collection of sufficient cells for at least two transplants.
The median number of CD34+ cells harvested was compared between patients randomised to Tdc, Rdc and KRdc and those who received 4, 5-6 or >6 cycles of induction. Mann-Whitney U Tests were used to compare groups. Only patients achieving >=VGPR to initial induction, completing >=4 cycles and proceeding directly to ASCT were included in this analysis to avoid any impact of response or intensification therapy on harvest outcome.
Results
Of the 1543 patients included, 521 had received Tdc (51.0% of all patients randomised to Tdc), 610 Rdc (59.7%), 412 KRdc (78.3%). Of these patients 88.4% underwent harvest (Tdc 86.9%, Rdc 87.5%, KRdc 91.5%).
The median number of CD34+ cells harvested was lower for those who had received lenalidomide compared to thalidomide. Patients who received Tdc harvested a median 4.6x10^6/kg CD34+ cells, Rdc 4.1, KRdc 4.2 (Rdc vs Tdc p=0.0002, KRdc vs Rdc p=0.1766, KRdc vs Tdc p=0.0210). There was also a reduction in the median CD34+ cells harvested for patients requiring >6 cycles of induction to achieve maximum response prior to harvest. 4 cycles 4.5 x10^6/kg CD34+ cells, 5-6 cycles 4.2, >6 cycles 4.1 (4 vs 5-6 p=0.1212, 5-6 vs >6 p=0.1839, 4 vs >6 p=0.0262).
The reduction in CD34+ cells with increasing number of induction cycles appeared greater for those patients who received lenalidomide induction. Tdc: 4 cycles 4.9 x10^6/kg CD34+ cells, 5-6 cycles 4.6, >6 cycles 4.6. Rdc: 4 cycles 4.4, 5-6 cycles 4.0, >6 cycles 3.5. KRdc: 4 cycles 4.4, 5-6 cycles 4.1, >6 cycles 3.9. This corresponded to a reduction in the proportion of patients meeting the threshold for two ASCTs both between therapies and with increasing cycles. Tdc: 4 cycles 63.0%, 5-6 cycles 60.2%, >6 cycles 61.4%. Rdc: 4 cycles 54.3%, 5-6 cycles 47.4%, >6 cycles 46.2%. KRdc: 4 cycles 60.9%, 5-6 cycles 49.3%, >6 cycles 41.7%.
Despite these differences, more than 96% of patients in all groups were considered to have enough stem cells and proceeded to first ASCT within the trial, with no differences between treatment groups.
Conclusion
Lenalidomide-based induction therapy was associated with lower median CD34+ cells harvested than thalidomide-based induction. This had no impact on the proportion of patients able to undergo first ASCT. The reduction in median CD34+ cells with lenalidomide was most marked when >4 cycles were administered. This should be considered when planning the timing of harvests, especially if storage of sufficient cells for two ASCTs is desired.
Keyword(s): Immunomodulatory thalidomide analog, Myeloma, Stem cell collection
Abstract: EP1259
Type: E-Poster Presentation
Session title: Stem cell transplantation - Clinical
Background
Autologous stem cell transplant (ASCT) remains standard of care for eligible newly diagnosed myeloma patients (TE NDMM). Induction prior to ASCT frequently includes lenalidomide, reported to have an adverse effect on peripheal blood stem cell (PBSC) harvest in some studies.
Aims
The UK NCRI Myeloma XI/+ study compared induction combinations including thalidomide or lenalidomide giving the opportunity to compare PBSC harvests between patients treated with different immunomodulatory agents.
Methods
TE NDMM patients were randomised to triplet combinations, thalidomide or lenalidomide plus dexamethasone and cyclophosphamide (Tdc/Rdc) or the quadruplet combination carfilzomib+Rdc (KRdc). Induction was given for a min. of 4 cycles but continued to max. response. Patients who received Tdc/Rdc and achieved a max. response less than VGPR underwent response-adapted intensification therapy.
PBSC harvest was planned to occur after the completion of induction+/-intensification. Stem cell mobilisation and harvest was performed according to local practice with advice to aim for the collection of sufficient cells for at least two transplants.
The median number of CD34+ cells harvested was compared between patients randomised to Tdc, Rdc and KRdc and those who received 4, 5-6 or >6 cycles of induction. Mann-Whitney U Tests were used to compare groups. Only patients achieving >=VGPR to initial induction, completing >=4 cycles and proceeding directly to ASCT were included in this analysis to avoid any impact of response or intensification therapy on harvest outcome.
Results
Of the 1543 patients included, 521 had received Tdc (51.0% of all patients randomised to Tdc), 610 Rdc (59.7%), 412 KRdc (78.3%). Of these patients 88.4% underwent harvest (Tdc 86.9%, Rdc 87.5%, KRdc 91.5%).
The median number of CD34+ cells harvested was lower for those who had received lenalidomide compared to thalidomide. Patients who received Tdc harvested a median 4.6x10^6/kg CD34+ cells, Rdc 4.1, KRdc 4.2 (Rdc vs Tdc p=0.0002, KRdc vs Rdc p=0.1766, KRdc vs Tdc p=0.0210). There was also a reduction in the median CD34+ cells harvested for patients requiring >6 cycles of induction to achieve maximum response prior to harvest. 4 cycles 4.5 x10^6/kg CD34+ cells, 5-6 cycles 4.2, >6 cycles 4.1 (4 vs 5-6 p=0.1212, 5-6 vs >6 p=0.1839, 4 vs >6 p=0.0262).
The reduction in CD34+ cells with increasing number of induction cycles appeared greater for those patients who received lenalidomide induction. Tdc: 4 cycles 4.9 x10^6/kg CD34+ cells, 5-6 cycles 4.6, >6 cycles 4.6. Rdc: 4 cycles 4.4, 5-6 cycles 4.0, >6 cycles 3.5. KRdc: 4 cycles 4.4, 5-6 cycles 4.1, >6 cycles 3.9. This corresponded to a reduction in the proportion of patients meeting the threshold for two ASCTs both between therapies and with increasing cycles. Tdc: 4 cycles 63.0%, 5-6 cycles 60.2%, >6 cycles 61.4%. Rdc: 4 cycles 54.3%, 5-6 cycles 47.4%, >6 cycles 46.2%. KRdc: 4 cycles 60.9%, 5-6 cycles 49.3%, >6 cycles 41.7%.
Despite these differences, more than 96% of patients in all groups were considered to have enough stem cells and proceeded to first ASCT within the trial, with no differences between treatment groups.
Conclusion
Lenalidomide-based induction therapy was associated with lower median CD34+ cells harvested than thalidomide-based induction. This had no impact on the proportion of patients able to undergo first ASCT. The reduction in median CD34+ cells with lenalidomide was most marked when >4 cycles were administered. This should be considered when planning the timing of harvests, especially if storage of sufficient cells for two ASCTs is desired.
Keyword(s): Immunomodulatory thalidomide analog, Myeloma, Stem cell collection