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Multiple myeloma RVd (lenalidomide bortezomib dexamethasone) PETHEMA overview

 RVd protocols on eviQ:

There are several RVd protocols on eviQ. This reflects current Australian clinical practice with variations in dosing schedules, indications and treatment intent. Please ensure you are viewing the correct protocol.

eviQ will closely review the clinical need for multiple versions of the RVd protocol to rationalise and consolidate in the future. 

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Treatment overview diagram 

RVd: lenalidomide/bortezomib/dexamethasone, 

© Blood 2019

Note: Combination bortezomib and lenalidomide cannot be administered under the PBS past cycle six utilising the RVd 28-day (four weekly) protocol.

Multiple myeloma induction RVd (lenalidomide bortezomib dexamethasone) PETHEMA 

Duration:
28 days
Cycles:
6
 

Patient information

Multiple myeloma consolidation RVd (lenalidomide bortezomib dexamethasone) PETHEMA 

Duration:
28 days
Cycles:
2
 
 

Patient information

Note: Use of a bone modifying agent (BMA) should be considered in all patients with symptomatic myeloma requiring treatment. For patients with newly diagnosed symptomatic myeloma, zoledronic acid, pamidronate or denosumab should be considered for monthly administration (adjust for kidney dysfunction where appropriate) for up to 2 years. A longer duration of therapy may be appropriate (MRC M IX trial).r
For more information, please see the following protocols:

  • Newly diagnosed multiple myeloma patients who are eligible for autologous stem cell transplantation

eviQ is currently updating the way information is presented in the evidence section to improve usability, consistency and facilitate easier update and maintenance. An updated evidence template is being implemented in a staged approach, first across new protocols, then existing protocols as they are reviewed. Find out more

Bortezomib/lenalidomide/dexamethasone (RVd) has not been compared to other triplet induction regimens (cyclophosphamide, bortezomib, dexamethasone [CyBorD or VCD] and bortezomib, thalidomide, dexamethasone [VTD]) in a phase III randomised study. However, on the basis of cross-trial comparisons of response rates and toxicity, the expert reference panel supports the use of RVd as induction treatment for transplant-eligible patients with multiple myeloma (MM). 

The dosing schedule in this eviQ protocol is based on the phase III study, PETHEMA/GEM2012, comparing 2 autologous stem cell transplant (ASCT) conditioning regimens (IV busulfan with melphalan vs. melphalan).r Patients in both arms of this study received 6 cycles of RVd induction, followed by ASCT and then 2 cycles of RVd consolidation.

Efficacy

In the PETHEMA/GEM2012 study, grouped response analysis of induction, transplant, and consolidation were reported. Responses deepened over time; in patients who initiated cycle 6 of induction (n = 426), the rates of a very good partial response (VGPR) or better were 55.6% by cycle 3, 63.8% by cycle 4, 68.3% by cycle 5, and 70.4% after induction. The complete response (CR) rate of 33.4% after induction in the intention-to-treat (ITT) population, which was similar in the 92 patients with high-risk cytogenetics (34.8%), also deepened with further treatment (44.1% after ASCT and 50.2% after consolidation). Rates of undetectable minimal residual disease (median 3 x 10-6 sensitivity) in the ITT population also increased from induction (28.8%) to transplant (42.1%) and consolidation (45.2%).r

Figure - Response ratesr

© Blood 2019

Toxicity

A summary of the toxicities associated with this protocol are included in the table below. The most clinically significant toxicities for this treatment are peripheral neuropathy and haematological adverse events. During induction, peripheral neuropathy was reported in 38% of patients and was grade 3/4 in 3.9% using RVd in the PETHEMA/GEM2012 study. Haematological grade 3/4 events were common in patients, including neutropenia (12.9%) and thrombocytopenia (6.3%).r

During induction, 14 patients (3.1%) had one or more treatment-emergent adverse event (TEAE) leading to discontinuation (cardiac disorders [1.1%] and infections [0.9%]), and 9 patients (2%) died due to TEAEs. Dose modifications were reported for bortezomib (32.1%), lenalidomide (26.4%) and dexamethasone (11.4%). The most common TEAEs leading to dose reduction or interruption of bortezomib was peripheral neuropathy and, for lenalidomide, were neutropenia and skin toxicity.r

During consolidation, the most common haematological TEAEs during consolidation were neutropenia (grade 3/4 10.5%) and thrombocytopenia (grade 3/4 9.9%), and the most common non-haematological TEAE was peripheral neuropathy (7.6% all grades, grade 3/4 0.3%). Dose modifications were reported for bortezomib (26.6%), lenalidomide (18.2%) and dexamethasone (6.8%).r

Table 1 - Adverse events through inductionr 

© Blood 2019

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Version 1

Date Summary of changes
27/09/2021 New protocol discussed at the Haematology reference committee meeting. Discussion continued over email and approved for publication. For review in 1 year.
14/10/2022 Reviewed by Haematology Reference Committee.
  • Note regarding bone modifying agents added in treatment schedule with links to protocols
  • Link to Medical Scientific Advisory Group (MSAG) Clinical Practice Guideline Multiple Myeloma updated
  • Minor updates to grammar and spelling

Review in 2 years.
28/10/2024 Protocol reviewed electronically by the Haematology reference committee. Nil changes made. Review in 2 years.

The information contained in this protocol is based on the highest level of available evidence and consensus of the eviQ reference committee regarding their views of currently accepted approaches to treatment. Any clinician (medical oncologist, haematologist, radiation oncologist, medical physicist, radiation therapist, pharmacist or nurse) seeking to apply or consult this protocol is expected to use independent clinical judgement in the context of individual clinical circumstances to determine any patient's care or treatment. While eviQ endeavours to link to reliable sources that provide accurate information, eviQ and the Cancer Institute NSW do not endorse or accept responsibility for the accuracy, currency, reliability or correctness of the content of linked external information sources. Use is subject to eviQ’s disclaimer available at www.eviQ.org.au

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First approved:
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The currency of this information is guaranteed only up until the date of printing, for any updates please check:

https://www.eviq.org.au/p/3936

27 Jun 2025