p53 deletion by fluorescence in situ hybridization (FISH) has been reported in about 10% of newly diagnosed patients (pts) with multiple myeloma (MM) and has been associated with a poor prognosis. Previous data from our centre has demonstrated that the progression-free survival (PFS) and overall survival (OS) of these pts after a single autologous stem cell transplant (ASCT) is only 16.9 and 48.2 months, respectively, compared to 24.4 and 76.6 mos, respectively, in all pts transplanted during the same time period (

Mikhael et al, Blood 2007; 110: abstract 953
). Minimal information is available on the treatment (Tx) and course of these pts following disease progression. Therefore, we performed a retrospective review of all MM pts treated at our institution who were found to have p53 deletion. We identified 31 pts with relapsed/refractory (rel/ref) MM with this cytogenetic abnormality. At diagnosis, median age was 54 years (range, 31–70), hemoglobin 97 g/L (range, 67–149), creatinine 96 μmol/L (range, 28–1751), beta 2-microglobulin 314 nmol/L (range, 225–437), CRP 3 mg/L (range, 2–7) and LDH 205 U/L (range, 82–478); 58% were male. Immunoglobulin subtypes included: IgG (14 pts), IgA (8 pts), IgD (2 pts) and light chain only (7 pts). Concomitant cytogenetic abnormalities included 13q deletion in 68% and t(4;14) in 67% of pts evaluable. Thirty-nine percent developed plasma cell leukemia (PCL) at some point in the disease course, which was associated with a poor OS (p=0.005). All but 5 had undergone prior ASCT with a median time from diagnosis to ASCT of 8 (95% CI, 4–145) mos. Txs given for rel/ref MM consisted of the following regimens: thalidomide-based in 15, bortezomib-based in 12, lenalidomide-based in 11, alkylating agents in 9 and steroids only in 5 pts, and other regimens (D-PACE or investigational drugs) in 7 pts. The median follow-up from diagnosis in these pts is 45 (95% CI, 4–145) mos. The overall response rate (≥PR) (ORR), median PFS and median OS from the start of each regimen is shown below.

AgentMedian duration of Tx (mos)ORR(%)Median PFS (mos)Median OS (mos)
Thalidomide 6.2 20% 5.0 11.9 
Bortezomib 5.2 50% 5.6 36.1 
Lenalidomide 10.6 60% 4.8 36.1 
Alkylating agents 6.0 11% 5.1 30.0 
Steroids 1.9 20% 1.9 33.4 
Other 2.2 43% 6.3 33.4 
AgentMedian duration of Tx (mos)ORR(%)Median PFS (mos)Median OS (mos)
Thalidomide 6.2 20% 5.0 11.9 
Bortezomib 5.2 50% 5.6 36.1 
Lenalidomide 10.6 60% 4.8 36.1 
Alkylating agents 6.0 11% 5.1 30.0 
Steroids 1.9 20% 1.9 33.4 
Other 2.2 43% 6.3 33.4 
View Large

We conclude: 1) Median PFS in pts with the p53 deletion is less than 6 months, with an OS of 2.5–3 yrs; 2) novel agents other than thalidomide produce the highest ORR in rel/ref MM with p53 deletion; 3) the short OS in the thalidomide group is likely related to the unavailability of other novel agents for subsequent relapses, as the majority of the pts were treated before 2004; 4) better strategies/drugs are required for these pts.

Topics:
multiple myeloma, brachial plexus neuritis, autologous stem cell transplant, thalidomide, alkylating agents, bortezomib, disease progression, lenalidomide, steroids, antigens, cd98 light chains

Disclosures: Reece:Millennium Pharmaceuticals Inc: Honoraria, Research Funding; Ortho Biotech Canada: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Chen:Ortho Biotech Canada: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding. Mikhael:Ortho Biotech Canada: Honoraria; Celgene: Honoraria; Amgen: Honoraria.

Author notes

Corresponding author

2008, The American Society of Hematology
2008
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