Clinical Trial Summary
Multiple myeloma (MM) is a plasma cell neoplasm representing the second most common type of
hematologic tumor after lymphomas. The incorporation of novel agents such as bortezomib,
lenalidomide, or thalidomide into first-line treatment as well as in relapse settings has led
to a significant improvement in survival rates for MM patients, which have doubled in the
last 5-7 years (1,2). However, except for a small percentage of patients (10-30%)(3) that may
achieve a cure after first-line treatment, in the majority of cases, MM behaves as an
incurable disease whose clinical course is characterized by repeated relapses, shorter and
shorter periods of remission, and by becoming refractory to succesive treatments (bortezomib
or lenalidomide). In this situation, survival is generally less than 9 months, which
underscores the need to develop new drugs for MM patients Pomalidomide, a third-generation
immunomodulatory drug (IMiD), has demonstrated efficacy in patients with relapsed and
refractory MM, with an overall response rate that fluctuates between 30-60% depending on
whether it is administered in combination with low-dose dexamethasone or in association with
treatment with a cytostatic agent such as cyclophosphamide.
In clinical trial CC-4047-MM-003, treatment with pomalidomide and low-dose dexamethasone in
patients with relapsed and refractory MM or those intolerant to bortezomib or lenalidomide
was a successful rescue treatment in 30% of patients with a median progression-free survival
of 4 months. The association of cyclophosphamide at dose of 400mg/day on days 1, 8, and 15 of
each cycle is able to increase the overall response rate from 39% for combination
pomalidomide-dexamethasone to up to 65% for the triple regimen (pomalidomide,
cyclophosphamide, dexamethasone - POMCIDEX), as well as the median PFS from 4.4 mo. to 9.2
mo. respectively. As well, the tolerance and safety profiles of the triple combination
pomalidomide, cyclophosphamide, and dexamethasone were acceptable.
The association of bortezomib with pomalidomide-dexamethasone also increases the overall
response rate (85%) and prolongs PFS (10.7 months).
The BiRD study (lenalidomide, dexamethasone, and clarithromycin) suggests that clarithromycin
intensifies the effect of corticosteroids, increasing their anti-myeloma effect . A study
evaluating the combination of clarithromycin with pomalidomide and low-dose dexamethasone in
RRMM patients showed an overall response rate of 57% and clinical benefit rate (considered
equal or superior to minor response) of 66%.
Since July 2014, pomalidomide (Imnovid®) in combination with dexamethasone has been approved
for the treatment of adult patients with relapsed and refractory MM who have received at
least two prior lines of therapy (including bortezomib and lenalidomide) and who have shown
progressive disease to the last line of treatment.
In Spain in January of 2015, and in the Spanish Myeloma Group (GEM) context, we implemented
clinical practice guidelines for the treatment of RRMM patients who are candidates for
pomalidomide treatment with a triple therapy combination pomalidomide + cyclophosphamide +
low-dose dexamethasone (POMCIDEX) (Appendix 1). The goal of the clinical practice guidelines
was to increase the overall response rate, quality of response, and progression-free survival
in patients treated with POMCIDEX. In patients with suboptimal response (defined as stable
disease in the first 3 cycles, or inferior to partial response after six cycles according to
International Myeloma Working Group Uniform Response Criteria [7]), clarithromycin can be
added to their treatment at a dose of 500mg/12hrs on days 1-28 of each cycle. Treatment can
be administered until disease progression, unacceptable toxicity, or based on patient
decision.
Keeping in mind the time that has passed since the approval of pomalidomide for use in Spain
and the publication of the clinical practice guidelines, we believe it is now time for a
retrospective evaluation of the results of the therapeutic guidelines for Spanish MM patients
and to review the viability of the recommendations contained in the guidelines with respect
to compliance with the same, and effectiveness of the planned course of treatment. Once the
viability of the proposed therapy regimen has been evaluated, other analyses for the purpose
of studying the clinical results of treatment can be carried out as a separate analysis.
The therapeutic paradigm for MM is rapidly changing due to the availability of new drugs for
the treatment of patients with refractory or relapsed disease, making clinical decisions more
challenging. For this reason, the availability of data obtained from real-life settings,
outside of clinical trials, is essential in order to choose the appropriate treatment for
each patient
This is a national, multicentre, observational, retrospective, open-label, non-randomized,
non-interventional study to evaluate the degree of compliance at PETHEMA centres in Spain
with the clinical practice guidelines proposed by the Spanish Myeloma Group for the treatment
of relapsed and refractory MM with POMCIDEX.
In this study, all patients will be included retrospectively who met the inclusion criteria
for the GEM clinical practice guidelines and who were treated with POMCIDEX. The period of
retrospective data collection will be from 01/01/2015 to 01/04/2018.
The period of data collection for the study includes a maximum period of three months to
allow each centre to collect the necessary clinical and demographic data for each patient in
order to fulfill the different study objectives. Patient data will be anonymized and recorded
in the electronic Case Report Form (eCRF) using the RedCap platform. Afterward, data
cleansing and verification will be carried out on all data recorded by the study
investigators. This procedure will be carried out in the six months after database lock.
Once the process of recording and verification of patient data is complete, extraction and
statistical analysis of the data will be carried out.