Written in Blood
and recipient cytomegalovirus serostatus,
donor–recipient HLA-match was the only
donor factor associated with mortality.
Dr. Kollman and colleagues also analyzed hematologic recovery associated with
donor–recipient variables, finding that the
likelihood of neutrophil recovery was lower
after transplantation of allografts from female donors and from donors mismatched
at two or more HLA-loci (odds ratio [OR]
= 1.26; 95% CI 1.06-1.51; p=0.007). For
degree of HLA-match, likelihood of recovery was lower after 6/8 (OR=0.72; 95%
CI 0.55-0.93; p=0.01) and 5/8 (OR=0.55;
95% CI 0.40-0.74; p<0.001), but not 7/8
HLA-matched transplants (OR=0.85; 95%
CI 0.69-1.04; p=0.11), compared with 8/8
HLA-matched transplants.
The risk of grade 2-4 GVHD was
higher in older donors, though this rate
was only significantly different between
donors aged 18-32 and those ≥33 years
(p=0.01), not between donors ≥50 years
and 33-50 years.
“Our analyses support [that] donor
parity, rather than the traditional donor–recipient sex match combination,
is associated with greater incidence of
chronic GVHD, non-relapse mortality,
and relapse,” they added. “However, any
benefit from lower relapse risks associated with transplantation of grafts from
female parous donor was negated by
higher non-relapse mortality.”
The current analyses revealed that sex,
parity, and cytomegalovirus serostatus
were not associated with survival.
“Patients receiving transplants from
younger HLA-matched donors had
the best survival rates after adjusting
T:7”
5.6 Second Primary Malignancies
In clinical trials in patients with multiple myeloma receiving REVLIMID an
increase of invasive second primary malignancies notably AML and MDS
have been observed. The increase of cases of AML and MDS occurred
predominantly in NDMM patients receiving REVLIMID in combination with
oral melphalan (frequency of 5.3%) or immediately following high dose
intravenous melphalan and ASCT (frequency of up to 5.2%). The
frequency of AML and MDS cases in the REVLIMID / dexamethasone
arms was observed to be 0.4%. Cases of B-cell malignancies (including
Hodgkin’s Lymphomas) were observed in clinical trials where patients
received lenalidomide in the post-ASCT setting.
Patients who received REVLIMID-containing therapy until disease
progression did not show a higher incidence of invasive SPM than
patients treated in the fixed duration REVLIMID-containing arms. Monitor
patients for the development of second primary malignancies. Take into
account both the potential benefit of REVLIMID and the risk of second
primary malignancies when considering treatment with REVLIMID.
5.7 Hepatotoxicity
Hepatic failure, including fatal cases, has occurred in patients treated with
lenalidomide in combination with dexamethasone. In clinical trials, 15% of
patients experienced hepatotoxicity (with hepatocellular, cholestatic and
mixed characteristics); 2% of patients with multiple myeloma and 1% of
patients with myelodysplasia had serious hepatotoxicity events. The
mechanism of drug-induced hepatotoxicity is unknown. Pre-existing
viral liver disease, elevated baseline liver enzymes, and concomitant
medications may be risk factors. Monitor liver enzymes periodically.
Stop REVLIMID upon elevation of liver enzymes. After return to baseline
values, treatment at a lower dose may be considered.
5.8 Allergic Reactions
Angioedema and serious dermatologic reactions including StevensJohnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have
been reported. These events can be fatal. Patients with a prior history of
Grade 4 rash associated with thalidomide treatment should not receive
REVLIMID. REVLIMID interruption or discontinuation should be considered
for Grade 2-3 skin rash. REVLIMID must be discontinued for angioedema,
Grade 4 rash, exfoliative or bullous rash, or if SJS or TEN is suspected
and should not be resumed following discontinuation for these reactions.
5.9 Tumor Lysis Syndrome
Fatal instances of tumor lysis syndrome have been reported during
treatment with lenalidomide. The patients at risk of tumor lysis syndrome
are those with high tumor burden prior to treatment. These patients
should be monitored closely and appropriate precautions taken.
5.10 Tumor Flare Reaction
Tumor flare reaction has occurred during investigational use of lenalidomide
for CLL and lymphoma, and is characterized by tender lymph node
swelling, low grade fever, pain and rash. REVLIMID is not indicated and
not