VRD Bortezomib Lenalidomide Dexamethasone Multiple Myeloma Protocol V1.0

THE CLATTERBRIDGE CANCER CENTRE NHS FOUNDATION TRUST
Systemic Anti Cancer Therapy Protocol
VRD – Bortezomib, Lenalidomide & Dexamethasone

Multiple Myeloma
PROTOCOL REF: MPHAVRDHA

(Version No: 1.0)
Approved for use in:

 Induction therapy for Multiple Myeloma
 EGOG PS 0-2
 This combination is not funded by NHS England. Individual funding must be agreed
prior to initiation.
Blueteq registration is not required
Dosage:
Drug Dose Route Frequency
Bortezomib 1.3mg/m2 S/C Day 1, 4, 8 and 11 of a 21 day cycle
Lenalidomide 25mg Oral Days 1 to 14 of a 21 day cycle
Dexamethasone 20mg Oral Days 1,2,4,5,8,9,11 and 12
Maximum of 6 cycles (21 day cycle).
Administration and Counselling Points:

 Anticoagulation is required throughout treatment due to thrombotic effect of
Lenalidomide.
 There must be a gap of at least 72 hours between bortezomib doses.
 The prescriber must inform male and female patients about the expected teratogenic
risk and the strict pregnancy prevention measures as specified in the pregnancy
prevention programme and provide patients with appropriate patient educational
brochure and patient card.
Issue Date: 9th October 2020
Page 1 of 9 Protocol reference: MPHAVRDHA
Review Date: October 2023
Author: Aileen McCaughey Authorised by: Drug & Therapeutics Committee Version No: 1.0
Anti-emetic risk:
Mildly emetogenic
Supportive treatments:
 Allopurinol 300mg daily (first cycle only)
 Anticoagulation – options include prophylactic dose of low molecular weight heparin
(LWMH) and treatment dose of LMWH in high risk patients. For patients established on
DOACs, patients may continue DOAC treatment or be switched to a LMWH.
 Aciclovir PO 400mg twice daily
 Co-trimoxazole PO 480mg daily
 Nystatin 1ml topically four times a day or fluconazole PO 50mg daily
 Metoclopramide 10mg three times a day when required for up to 7 days
 Omeprazole 20mg daily
Extravasation risk:
Bortezomib – non-vesicant
Interactions:
Lenalidomide
Agents that may increase the risk of thrombosis, such as HRT should be used with caution in
multiple myeloma patients receiving lenalidomide with dexamethasone
Bortezomib
A drug-drug interaction study assessing the effect of ketoconazole, a potent CYP3A4
inhibitor, on the pharmacokinetics of bortezomib (injected intravenously), showed a mean
bortezomib AUC increase of 35% (CI90% [1.032 to 1.772]) based on data from 12 patients.
Therefore, patients should be closely monitored when given bortezomib in combination with
potent CYP3A4 inhibitors (e.g. ketoconazole, ritonavir).
A drug-drug interaction study assessing the effect of rifampicin, a potent CYP3A4 inducer, on
the pharmacokinetics of bortezomib (injected intravenously), showed a mean bortezomib
AUC reduction of 45% based on data from 6 patients. Therefore, the concomitant use of

bortezomib with strong CYP3A4 inducers (e.g., rifampicin, carbamazepine, phenytoin,

phenobarbital and St. John's Wort) is not recommended, as efficacy may be reduced.
Treatment schedule:
Day Drug Dose Route Diluent and rate
1 Lenalidomide 25mg PO Nocte
Dexamethasone 20mg PO
Bortezomib 1.3mg/m2 S/C
6, 7 Lenalidomide 25mg PO Nocte
13
to Lenalidomide 25mg PO Nocte
14

Main toxicities:
Thrombocytopenia, neutropenia, anaemia, nausea, vomiting, diarrhoea, peripheral
neuropathy, drowsiness and venous thromboembolism.

Investigations and treatment plan:
Cycle Cycle Cycle Cycle

Pre Ongoing
1+ D1 1+ D4 1+ D8 1+ D11
Informed consent x
Clinical Assessment x x
Lenalidomide prescription authorization
form x
SACT Assessment (including
performance status toxicity assessment) x x x x
FBC x x
U&E, LFTs and calcium profile x x
Hepatitis B core antibody and surface
antigens & Hep C & HIV 1+2 x
Dental Assessment x If clinically indicated
HbA1c and glucose x Repeat if clinically indicated

Serum Igs/electrophoresis/serum
free light chains (if indicated) x x
Neurological assessment (for
neuropathy) – performed at medical x x
review
Blood pressure x x x x x
Weight x x
Height x
If clinically indicated. Repeat each cycle if
Pregnancy test x women of childbearing potential
Imaging as per NICE/network
guidance and clinical indication x To restage as indicated

Dose Modifications and Toxicity Management:

Haematological toxicity:
Bortezomib:
Proceed on day 1 if-
ANC ≥ 0.5 x 109/L Plt ≥ 25 x 109/L
Once the symptoms of the toxicity have resolved, bortezomib treatment may be re-
initiated at a 25% reduced dose (1.3 mg/m2 reduced to 1.0 mg/m2; 1.0 mg/m2 reduced
to 0.7 mg/m2). If the toxicity is not resolved or if it recurs at the lowest dose,
discontinuation of bortezomib must be considered unless the benefit of treatment clearly
outweighs the risk.
Lenalidomide:
Treatment should not normally be given if ANC < 0.5 x 109/L, and/or platelet count < 30
x 109/L. If low counts are thought to be due to myeloma per se, the use of G-CSF and
platelet support should be considered.
Dose adjustments, as summarised below, are recommended to manage grade 3 or 4

neutropenia or thrombocytopenia, or other grade 3 or 4 toxicity judged to be related to
lenalidomide.
Dose reductions below are based on a starting dose of 25 mg/day. Please be aware
that some patients can start a reduced dose from cycle 1
Thrombocytopenia:
When Platelets Recommended Course
First Fall to <30 x109/L Interrupt lenalidomide treatment
Return to >30 x109/L Resume lenalidomide at 15mg a day
For each subsequent deop below 30 Interrupt lenalidomide treatment
x109/L
Return to >30 x109/L Resume lenalidomide at next lower dose
level. Do not dose reduce below 5mg
daily

Neutropenia:
When Neutrophils Recommended Course
First fall to < 0.5 x 109/L Interrupt lenalidomide treatment.
Administer G-CSF for 3 days and recheck
FBC.
Return to ≥ 0.5 x 109/L when neutropenia Resume lenalidomide at 25 mg once daily
is the only observed toxicity
Return to ≥ 0.5 x 109/L when dose- Resume lenalidomide at 15 mg once daily
dependent haematological toxicities other
than neutropenia are observed
For each subsequent drop below < 0.5 x Interrupt lenalidomide treatment.
109/L Administer G-CSF for 3 days.
Return to ≥ 0.5 x 109/L Resume lenalidomide at next lower dose
level (i.e. if was on 15 mg, reduce to 10
mg - or if was on 10 mg, reduce to 5
mgonce daily). Do not dose below 5 mg
once daily.
Dosing in renal and hepatic impairment:

Lenalidomide
Renal Hepatic
CrCl 30 – 49 mL/min 10mg once daily* No formal studies. No specific dose
CrCl < 30 mL/min, no dialysis 15 mg every recommendations
other day**
CrCl < 30 mL/min, requiring dialysis 5 mg
once daily***
*Can increase to 15mg OD if no response and patient tolerating
** Can increase to 10mg OD if no response and patient tolerating
*** On dialysis day, administer dose after dialysis
Bortezomib
Renal
No dose adjustments required but bortezomib should be administered after dialysis.
Hepatic
Liver function Dose adjustment
Moderate to severe impairment Reduce to 0.7mg/m2

Peripheral Neuropathy
Bortezomib
If there are symptoms of peripheral neuropathy the dose reduction schedule below must
be invoked. Bortezomib should be stopped if symptoms or signs progress despite this
Grade 1 with no pain or loss of Dose adjustment

function
Grade 1 with pain or grade 2 Reduce to 1.0mg/m2 or reduce to 1.3mg/m2 weekly
(day 1 and 8)
Grade 2 with pain of grade 3 Withhold treatment until symptoms of toxicity have
resolved. When toxicity resolves re-initiate treatment
at 0.7mg/m2 weekly (day 1 and 8)
Grade 4 and/or severe Discontinue
autonomic neuropathy
Lenalidomide
Lenalidomide is structurally related to thalidomide, which is known to induce
neuropathy. However, published data suggests that significant neurotoxicity is
uncommon.
References:
1. Richardson PG, Weller E, Lonial S, Jakubowiak AJ, Jagannath S, Raje NS, et al.
Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with
newly diagnosed multiple myeloma. Blood. 2010 Aug 5;116(5):679-86.
2. Velcade ® Bortezomib eMC UK Summary of Product Characteristics, Janssen,
February 2019
3. Lonial S, Waller EK, Richardson PG, Jagannath S, Orlowski RZ, Giver CR, Jaye DL,
Francis D, Giusti S, Torre C, Barlogie B, Berenson JR, Singhal S, Schenkein DP,
Esseltine DL, Anderson J, Xiao H, Heffner LT, Anderson KC; SUMMIT/CREST
Investigators. Risk factors and kinetics of thrombocytopenia associated with bortezomib
for relapsed, refractory multiple myeloma. Blood. 2005 Dec 1;106(12):3777-84.
4. Jimenez-Zepeda VH, Reece DE, Trudel S, Chen C, Tiedemann R, Kukreti V.
Lenalidomide (Revlimid), bortezomib (Velcade) and dexamethasone for heavily
pretreated relapsed or refractory multiple myeloma. Leuk Lymphoma. 2013
Mar;54(3):555-60.

5. Richardson PG, Jagannath S, Jakubowiak AJ, Lonial S, Raje N, Alsina M, et al.

Phase II Trial of Lenalidomide, Bortezomib, and Dexamethasone In Patients (pts) with
Relapsed and Relapsed/Refractory Multiple Myeloma (MM): Updated Efficacy and
Safety Data After >2 Years of Follow-up. ASH Annual Meeting Abstracts 2010
November 19, 2010; 116(21): 3049.
6. Richardson PG, Weller E, Jagannath S, Avigan DE, Alsina M, Schlossman RL, et al.
Multicenter, phase I, dose-escalation trial of lenalidomide plus bortezomib for relapsed
and relapsed/refractory multiple myeloma. J Clin Oncol. 2009 Dec 1;27(34):5713-9.
7. Revlimid® (lenalidomide) 25mg capules.


VRD Bortezomib Lenalidomide Dexamethasone Multiple Myeloma Protocol V1.0

Uploaded by

Document Information

Original Title

Copyright

Available Formats

Share this document

Share or Embed Document

Sharing Options

Did you find this document useful?

Is this content inappropriate?

Copyright:

Available Formats

VRD Bortezomib Lenalidomide Dexamethasone Multiple Myeloma Protocol V1.0

Uploaded by

Copyright:

Available Formats

THE CLATTERBRIDGE CANCER CENTRE NHS FOUNDATION TRUST

Systemic Anti Cancer Therapy Protocol

VRD – Bortezomib, Lenalidomide & Dexamethasone

PROTOCOL REF: MPHAVRDHA

Approved for use in:

Blueteq registration is not required

Maximum of 6 cycles (21 day cycle).

Administration and Counselling Points:

Issue Date: 9th October 2020

bortezomib with strong CYP3A4 inducers (e.g., rifampicin, carbamazepine, phenytoin,

Issue Date: 9th October 2020

Issue Date: 9th October 2020

Investigations and treatment plan:

Cycle Cycle Cycle Cycle

HbA1c and glucose x Repeat if clinically indicated

Issue Date: 9th October 2020

Dose Modifications and Toxicity Management:

Dose adjustments, as summarised below, are recommended to manage grade 3 or 4

Issue Date: 9th October 2020

Dosing in renal and hepatic impairment:

Issue Date: 9th October 2020

Grade 1 with no pain or loss of Dose adjustment

Issue Date: 9th October 2020

5. Richardson PG, Jagannath S, Jakubowiak AJ, Lonial S, Raje N, Alsina M, et al.

Issue Date: 9th October 2020

You might also like