A recent British analysis of data from a major clinical trial found that thalidomide maintenance therapy did not have a uniformly positive impact on overall survival in multiple myeloma patients.

In fact, overall survival for patients in the trial who received thalidomide maintenance was slightly lower than overall survival for patients who did not receive maintenance therapy.  The difference, however, was not statistically significant.

In contrast, progression free survival was significantly longer for patients who received thalidomide maintenance compared to patients who were not on a maintenance regimen.

The study findings thereby highlight how progression free survival and overall survival do not always move in lockstep with one another.

The authors of the British study also found that the choice of relapse therapy had a significant impact on the survival of patients who received thalidomide maintenance therapy.  The impact was so significant that the authors believe thalidomide maintenance therapy would have shown a clear overall survival benefit if relapse therapies had been better selected.

Recent evidence suggests that thalidomide ^[1] (Thalomid) maintenance therapy may work to reduce or suppress residual cancer that may exist in patients following induction therapy.

The goal of the British analysis was to determine whether the suppression of residual cancer by thalidomide maintenance provides a subsequent improvement in survival.

The researchers noted that, although there have been trials of thalidomide maintenance in the past, results regarding survival have been conflicting.  They pointed out that differences in results between trials may reflect differences in patient subgroups (chromosomal abnormalities, relapsed/refractory, etc.) and the type of relapse therapy given following disease progression.

To further confirm the effect of thalidomide maintenance therapy, the British researchers retrospectively analyzed data from patients who had participated in the Phase 3 MRC Myeloma IX trial.

The Myeloma IX trial included 1,970 newly diagnosed multiple myeloma patients, mostly in the United Kingdom.  The goal of the trial was to compare the efficacy of the bisphosphonates Zometa ^[2] (zoledronic acid) and Bonefos ^[3] (clodronic acid) in myeloma patients (see related Beacon ^[4] news) while also exploring the efficacy and safety of several different myeloma treatment regimens.

Half of the Myeloma IX trial participants were randomly selected to receive maintenance treatment with thalidomide.  The other half of the trial participants received no maintenance therapy.  Patients who received thalidomide maintenance therapy did not necessarily receive thalidomide as part of their induction therapy.  The selection of patients for maintenance therapy was made without consideration of the patient’s induction therapy.

Patients received 50 mg of thalidomide during the first four weeks of maintenance therapy. The dose was then increased to 100 mg until disease progression if patients tolerated the higher dose.

When the researchers compared the progression-free survival of patients who had received thalidomide maintenance to those who had not, they found a significant improvement with thalidomide maintenance.  Specifically, the progression-free survival was 23 months for patients receiving thalidomide maintenance, compared to 15 months for patients not receiving maintenance.

The researchers also found that improvements to progression-free survival were observed whether or not patients had received thalidomide-based induction therapy.

The results were different, however, when the researchers turned their attention to overall survival.  Overall survival rates for the patients who received thalidomide maintenance were statistically no different from -- and often lower than -- the survival rates of patients who did not receive thalidomide maintenance.

The researchers therefore looked to see whether thalidomide maintenance had a different effect on patients with higher-risk chromosomal abnormalities compared to patients without such abnormalities.

And, in fact, there was a difference in outcomes.  Thalidomide maintenance had a significant negative impact on overall survival in patients with higher-risk chromosomal abnormalities.

In contrast, there was a trend -- not yet statistically significant -- to thalidomide maintenance having a positive impact on the overall survival of patients without higher-risk chromosomal abnormalities.

When the British researchers looked in greater depth into why some patients who had been on thalidomide maintenance therapy lived longer than others who had been on the same regimen, they found that the treatment patients received at relapse played a key role.  Patients who received either Revlimid ^[5] (lenalido­mide) or Velcade ^[6] (bortezomib) at relapse lived significantly longer than those who received other treat­ments.

Indeed, based on a mathematical model they developed, the authors of the current study believe that thalidomide maintenance would have demonstrated a significant positive impact on overall survival across all patients if the maintenance patients always received either Revlimid or Velcade at relapse.

Patients received thalidomide maintenance therapy for a median of seven months.  Fifty two percent of patients stopped therapy before disease progression due to the severity of side effects, the most common of which was peripheral neuropathy (nerve damage causing tingling in the hands and feet).

The study authors point out that greater differences in survival might have been observed between thalidomide and non-thalidomide maintenance groups if patients had been able to continue thalidomide therapy for longer periods of time.  They also suggest that drugs with fewer side effects, such as Revlimid, may produce better results.

For additional information, please see the study in the journal Blood ^[7] (abstract).