Upfront Tandem Autologous Stem Cell Transplant Is Superior to Autologous or Allogeneic Stem Cell Transplant After Failure of a 1st Autologous Transplant,

Abstract 4094

Disease progression remains the main cause of treatment failure after autologous stem cell transplant (SCT) in patients with multiple myeloma (MM). It is unclear what is the best salvage therapy after failure of a 1^st autologous SCT in MM.

We performed a retrospective study comparing 2^nd autologous (auto-auto) versus 2^nd allogeneic (auto-allo) SCT in patients progressing or relapsing after their 1^st autologous SCT and compare their outcomes with patients receiving sequential planned double autologous (tandem) SCT as part of their upfront therapy for MM.

The data was collected from CIBMT reports and medical records at Texas Transplant Institute from 2001 to 2010. Patient's characteristics and outcomes are described in table 1. Response to 1^st and 2^nd SCT was determined at 100 days post transplant and classified as good (stringent complete remission [sCR], complete remission [CR], very good partial remission [VGPR]) or poor (partial remission [PR], stable disease [SD] or progressive disease [PD]). All patients in the auto-allo group received a reduced intensity regimen. 20% of the patients in the auto-auto group received maintenance therapy after their 1^st transplant with either thalidomide or lenalidomide and 10% of the patients in the auto-allo group received maintenance therapy after their 1^st transplant either with thalidomide. None of the patients in the tandem group received maintenance therapy. The overall survival was calculated from the date of the 2^nd transplant to the known date of death in all groups. Patients in the auto-allo group (15.9 months) had a worse median survival than in the auto-auto group (39 months) with both of them having a worse survival compared to patients undergoing tandem transplants (64.3) (p value = 0.003) (FIGURE).

Table:

PATIENT CHARACTERISTICS AND OUTCOMES

.	Tandem (n=29) .	Auto-Auto (n=32) .	Auto-Allo (n=10) .
Median age, years (range)	62 (41–78)	62.5 (45–81)	54 (43–63)
Median days from diagnosis to 1st transplant	224.5 (93–1344)	226 (117–1074)	254.5 (101–416)
Median days from 1st to 2nd transplant	149 (99–189)	847 (210–4158)	350 (88–1281)
Median total CD34+ cell infused 1st transplant	3.29 (2–12)	5.87 (2–28)	6.03 (2–14)
2nd transplant	3.22 (2–9)	4.47 (2–19)	5.25 (3–11)
Median WBC engraftment	11 (9–13)	11 (9–47)	N/A
Median Platelet engraftment	16 (10–19)	15 (10–23)	N/A
Cytogenetics High Risk
	17%	3%	10%
ISS at 1st transplant I	31%	41%	40%
II	34%	12%	0
III	14%	6%	10%
ISS at 2nd transplant I	48%	53%	40%
II	17%	9%	0
III	10%	13%	10%
Response to 1st transplant Good	10%	63%	70%
Poor	80%	25%	20%
Response to 2nd transplant Good	52%	47%	30%
Poor	41%	41%	70%
Median Followup (months)	57.1 (3.4–76.7)	24.6 (10.5–87.8)	48.0 (31.9–64.0)
Maintenance Therapy after 1st transplant	0	28%	10%

.	Tandem (n=29) .	Auto-Auto (n=32) .	Auto-Allo (n=10) .
Median age, years (range)	62 (41–78)	62.5 (45–81)	54 (43–63)
Median days from diagnosis to 1st transplant	224.5 (93–1344)	226 (117–1074)	254.5 (101–416)
Median days from 1st to 2nd transplant	149 (99–189)	847 (210–4158)	350 (88–1281)
Median total CD34+ cell infused 1st transplant	3.29 (2–12)	5.87 (2–28)	6.03 (2–14)
2nd transplant	3.22 (2–9)	4.47 (2–19)	5.25 (3–11)
Median WBC engraftment	11 (9–13)	11 (9–47)	N/A
Median Platelet engraftment	16 (10–19)	15 (10–23)	N/A
Cytogenetics High Risk
	17%	3%	10%
ISS at 1st transplant I	31%	41%	40%
II	34%	12%	0
III	14%	6%	10%
ISS at 2nd transplant I	48%	53%	40%
II	17%	9%	0
III	10%	13%	10%
Response to 1st transplant Good	10%	63%	70%
Poor	80%	25%	20%
Response to 2nd transplant Good	52%	47%	30%
Poor	41%	41%	70%
Median Followup (months)	57.1 (3.4–76.7)	24.6 (10.5–87.8)	48.0 (31.9–64.0)
Maintenance Therapy after 1st transplant	0	28%	10%

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OVERALL SURVIVAL

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OVERALL SURVIVAL

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Forward stepwise Cox regression analysis was used to measure factors affecting overall survival. Factors used for analysis included age, cytogenetics (high risk = mutated p53, t(14;16), t(4;14), del 13), International Staging System (ISS) before 1^st and 2^nd SCT, use of maintenance therapy after 1^st SCT, days from diagnosis to 1^st SCT and days from 1^st to 2^nd SCT, CD34+ cells infused at 1^st and 2^nd SCT. Age and ISS of III at 2^nd transplant were identified as factors affecting survival in the auto-auto group (hazard ration of 1.081 and 5.700, respectively).

In conclusion, overall survival after salvage from 2^nd autologous stem cell transplant is longer than after a 2^nd allogeneic transplant. Upfront, planned tandem autologous stem cell transplant is superior to both salvage strategies. Larger, randomized trials are needed to confirm these results.