The Reduced Intensity Cvd Regimen: A Good Option with Well Balanced Efficacy/Toxicity Ratio for Elderly Patients with Poor Status Performance
Authors: Hajek Roman , Zahradova Lenka , Gregora Evzen , Schutzova Miroslava , Koza Vladimir , Pavlicek Petr , Pour Ludek , Krejci Marta , Sandecka Viera , Krivanova Andrea , Sahmani Mohammed Al , Kralova Dana , Adam Zdenek 
Published: October 2019

Abstract
Background: Bortezomib (Velcade) based regimens became a part of standard treatment in multiple myeloma (MM). Further optimization, focused on the favourable efficacy/toxicity ratio, is essential mainly for elderly patients (pts) and pts with poor performance status. These pts usually do not tolerate full dose of bortezomib and neuropathy in combination with severe fatigue are the most pronounced toxicities resulting in premature interruption of the treatment. As final consequence, these patients cannot fully benefit from the strong anti-myeloma potential of bortezomib. In this trial, we have evaluated the potential of combinative regimen CVD (cyclophosphamide, bortezomib, dexamethasone) reduced intensity (CVD senior; 50% reduction) in elderly pts and/or pts with poor status performance with relapsed MM. The results were compared with CVD junior regimen outcome used at the same time in pts aged <65 years and good status performance.
Patients and Methods: A total of 40 consecutive pts (21x CVD senior vs 19x CVD junior) were evaluated in period from February 2007 until June 2008. Treatment regimen CVD senior: bortezomib (1.3mg/m2, day 1,15); cyclophosphamide (50mg p.o. daily) and dexamethasone 20mg (day 1–4, 15–18). Treatment regimen CVD junior: bortezomib (1.3mg/m2, day 1,4,8,15); cyclophosphamide (500mg/m2 i.v., day 1,15) and dexamethasone 40mg (day 1–4, 15–18). Both regimens were received in 28 days interval. All pts received at least 4 cycles of CVD regimen or the treatment was stopped for progression while received less than 4 cycles. The baseline characteristics of pts for CVD senior vs junior are as follows: median age 68.8 (range 50.2–80.6) vs 58.9 years (range 47.4–78.4), (p<0,001); clinical stage according to Durie and Salmon I-10.0% vs 5.2%/II-15.0% vs 15.8%/III-75.0% vs 79.0% (p=0,855); number of previous treatment lines 1–9.5% vs 36.8%/2–52.4% vs 57.9%/3 or more−38.1% vs 5.3% (p=0,011); median Karnofski status was 80% vs 90% (p=0,016); median follow-up from the start of therapy was 10.5 vs 8 months (p=0.192). In addition to significantly higher age, higher pretreatment and lower Karnofski index in CVD senior group, there was also a trend to a higher frequency of clinical stage 3 according to ISS (38.5% vs 29.4%).
Results: The basic results for CVD senior vs junior are as follows: overall response (ORR=CR+PR) was 42.9% vs 61.1% including CR 4.8% vs 22.3%, VGPR 9.5% vs 11.1% and PR 28.6 vs 27.8% and progression 19.0% vs 11.1%. There was no difference (p=0,51) in overall response between groups but a higher total dose of bortezomib achieved by pts in each group resulted in a better response in both groups (p=0,009 for CVD senior; p=0,021 for CVD junior). Grade 3 or 4 AEs were more frequent in the CVD junior group (9.1% vs 28%; p=0.002), with an increase in haematologic event, fatigue and neuropathy. Grade 4 AEs were not observed in CVD senior group. Median number of cycles was 5 in both groups but dose of bortezomib was reduced in less frequency in CVD senior regimen [9.5% (2/21) vs 26.3% (5/19)]. In CVD senior group, medians for parameters of survival were as follows: TTP/PFS 6.6 months, DOR 6.6 and OS 9.0 months. Although medians of the same parameters were not achieved yet in CVD junior group, they did not achieved significant difference. Actual data will be presented.
Conclusion: The reduced CVD senior regimen is tolerated better than CVD junior. Duration of treatment and number of cycles was similar in both regimens. There was no difference in overall response but the higher total dose of bortezomib achieved by pts in each group resulted in a better response in both groups. The reduced intensity CVD regimen seems to be a good option for elderly pts with poor status performance with well balanced efficacy/toxicity ratio.