The Positive Effect of Consolidation Therapy in Multiple Myeloma
It always interesting to talk to fellow multiple myeloma patients and learn about different treatment regimens and experiences they have had compared to our own. A case in point is that some of us have had ‘high dose’ consolidation therapy before starting maintenance and others haven’t. The question arises naturally then, ‘What provides the best outcome for us ?’ Up until now the evidence of what is best has essentially been anecdotal and somewhat dependent on the preferences of the treating medical team. The following large study showed that consolidation made a big difference in depth of response, duration of response (but not when reviewed at 5 years)
Editor's note: Consolidation therapy means using the same therapy (typically) that was used during induction therapy. It is usually a combination of myeloma therapies used at the same dose and frequency as the induction therapy and is used for 2-12 months following a stem cell transplant. This is different from maintenance therapy that is usually a single therapy at a lower dose used for several years or indefinitely following stem cell transplant.
A head-to-head, large study has been completed in Europe, driven by the European Myeloma Network and headed by Dr. Pieter Sonneveld (Erasmus Medical Center Cancer Institute in the Netherlands). This is the FIRST randomized trial that prospectively studied the role of consolidation therapy for newly diagnosed myeloma patients. The study started out with close to 1,200 patients that were randomly assigned to one of two treatment groups. About 500 patients received treatment that did not involve a stem cell transplant, and about 700 underwent either single or tandem stem cell transplants. Upon completion of the initial treatment process 878 patients were again randomly assigned to either immediately start maintenance or to start a consolidation treatment followed by maintenance (both groups were nearly equal in size).
“Consolidation included two 28-day cycles of VRD, which consisted of IV or subcutaneous bortezomib dosed at 1.3 mg/m2 on days 1, 4, 8 and 11; lenalidomide dosed at 25 mg orally on days 1 through 21; and dexamethasone dosed at 20 mg orally on days 1, 2, 4, 5, 8, 9, 11 and 12. Maintenance consisted of lenalidomide 10 mg daily until disease progression or unacceptable toxicity. The consolidation and no-consolidation groups were balanced with regard to age (median, 58 years vs. 57 years), sex (male, 57% vs. 58%), International Staging System stage (stage I, 42% vs. 42%; stage II, 40% vs. 37%) and percentage of patients high-risk cytogenetics (22% vs. 22%).”
Patients were followed-up for a median period of 84 months. The results are very interesting:
- 59 % of patients in the ‘consolidation’ group achieved either stringent complete response or complete response, compared to 46 % in the no-consolidation group
- The patients in the ‘consolidation’ group showed better progression free (PFS) survival (59 months compared to 43 months)
- The ‘consolidation’ cohort had a higher 5-year PFS rate (50 % compared to 42 %)
- “Researchers observed the PFS benefit across most predefined subgroups — including those with International Staging System stage I to stage III disease and standard-risk cytogenetics — and regardless of treatment group assignment during first randomization.”
- The median period of Revlimid maintenance was 33 months and nearly 1/3 of the patients in the ‘maintenance’ cohort were still in maintenance 5 years after starting this stage of their treatment
- So far, no difference in Overall Survival has been noted yet but patients continue to be followed-up and this statistic will be updated in the future
- A similar percentage of patients in both groups developed secondary primary malignancies (not including skin cancers)
Those who would like to know more details can refer to the highlighted article. The long and the short conclusion of this study is that consolidation treatment before maintenance improves outcomes for transplant-eligible, newly diagnosed myeloma patients.