Thalidomide plus dexamethasone (thal/dex) and thalidomide alone (thal) as first line therapy for newly diagnosed myeloma (mm)

S Vincent Rajkumar, S. Hayman, Rafael Fonseca, Angela Dispenzieri, Martha Lacy, S. Geyer, L. Wellik, J. A. Lust, R. A. Kyle, P. R. Greipp, Thomas Elmer Witzig

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

Background: A phase II trial of Thal/Dex combination and Thai as first line therapy in new untreated MM with laboratory correlative studies (interim analysis). Methods: Patients (pts) with active MM were treated with the Thal/Dex combination. Pts with smoldering or indolent MM (SMM/IMM) were treated with Thai alone. Thai was given orally at a dose of 200 mg/day for 2 weeks, and then increased as tolerated by 200 mg/day every 2 weeks to a maximum dose of 800 mg/day. Dex was given orally at a dose of 40 mg/day orally on days 1-4, 9-12, 17-20 (odd cycles) and 40 mg/day days 1-4 (even cycles) repeated monthly. Response was defined as a decrease in serum and urine monoclonal (M) protein by 50% or greater. Bone marrow (BM) microvessel density (MVD) using immunostaining for CD34 was estimated by determining the average number of vessels in 3 hot spots at 400x magnification. BM angiogenesis was also visually graded as low, intermediate and high. Results: 42 pts (26 with active MM and 16 with smoldering/indolent MM) were studied. In the Thal/Dex arm, 2 pts had grade 3-4 skin toxicity among the first 7 pts treated, at Thai dose of 400mg. The Thal/Dex arm was then amended to stop dose escalation, and keep Thai dose constant at 200mg. An objective response was seen in 20 pts (77%) with active MM treated with Thal/Dex. The response rate was 86% with Thai dose escalation (6 of 7 pts), and 74% with Thai dose constant at 200mg (14 of 19 pts). Major grade 3-4 toxicities were rash in 3 pts, and sedation, constipation and myalgias in 1 pt each. In the SMM/IMM arm, 6 pts (38%) achieved a response with Thai alone. Median pre-treatment MVD was 27 in the active MM arm, and 7 in the SMM/IMM arm (p<0.001). Angiogenesis grade was high in 64% of active MM and 8% of SMM/IMM, (p<0.001). The proportion of pts with a high(l) PCLI was 67%, 9%, 0% for high, intermediate, and low grade angiogenesis respectively (p<0.001 ). No significant changes were observed in MVD following treatment; pre-treatment MVD and angiogenesis grade did not appear to be associated with response to therapy. Conclusions: Thal/Dex is strikingly effective as first line therapy (and an oral alternative to infusional VAD) for new, active MM. SMM/IMM pts also appear to achieve significant responses with Thai alone. However, these results are preliminary and responses/toxicities are still being evaluated and need further confirmation in the final analysis of this trial.

Original languageEnglish (US)
JournalBlood
Volume96
Issue number11 PART I
StatePublished - 2000

Fingerprint

Thalidomide
Dexamethasone
Toxicity
Bone
Microvessels
Skin
Therapeutics
Bone Marrow
Proteins
Myalgia
Constipation
Complementary Therapies
Exanthema
Urine

ASJC Scopus subject areas

  • Hematology

Cite this

Thalidomide plus dexamethasone (thal/dex) and thalidomide alone (thal) as first line therapy for newly diagnosed myeloma (mm). / Rajkumar, S Vincent; Hayman, S.; Fonseca, Rafael; Dispenzieri, Angela; Lacy, Martha; Geyer, S.; Wellik, L.; Lust, J. A.; Kyle, R. A.; Greipp, P. R.; Witzig, Thomas Elmer.

In: Blood, Vol. 96, No. 11 PART I, 2000.

Research output: Contribution to journalArticle

@article{ed5adcfae9494b3bb840891a57de5566,
title = "Thalidomide plus dexamethasone (thal/dex) and thalidomide alone (thal) as first line therapy for newly diagnosed myeloma (mm)",
abstract = "Background: A phase II trial of Thal/Dex combination and Thai as first line therapy in new untreated MM with laboratory correlative studies (interim analysis). Methods: Patients (pts) with active MM were treated with the Thal/Dex combination. Pts with smoldering or indolent MM (SMM/IMM) were treated with Thai alone. Thai was given orally at a dose of 200 mg/day for 2 weeks, and then increased as tolerated by 200 mg/day every 2 weeks to a maximum dose of 800 mg/day. Dex was given orally at a dose of 40 mg/day orally on days 1-4, 9-12, 17-20 (odd cycles) and 40 mg/day days 1-4 (even cycles) repeated monthly. Response was defined as a decrease in serum and urine monoclonal (M) protein by 50{\%} or greater. Bone marrow (BM) microvessel density (MVD) using immunostaining for CD34 was estimated by determining the average number of vessels in 3 hot spots at 400x magnification. BM angiogenesis was also visually graded as low, intermediate and high. Results: 42 pts (26 with active MM and 16 with smoldering/indolent MM) were studied. In the Thal/Dex arm, 2 pts had grade 3-4 skin toxicity among the first 7 pts treated, at Thai dose of 400mg. The Thal/Dex arm was then amended to stop dose escalation, and keep Thai dose constant at 200mg. An objective response was seen in 20 pts (77{\%}) with active MM treated with Thal/Dex. The response rate was 86{\%} with Thai dose escalation (6 of 7 pts), and 74{\%} with Thai dose constant at 200mg (14 of 19 pts). Major grade 3-4 toxicities were rash in 3 pts, and sedation, constipation and myalgias in 1 pt each. In the SMM/IMM arm, 6 pts (38{\%}) achieved a response with Thai alone. Median pre-treatment MVD was 27 in the active MM arm, and 7 in the SMM/IMM arm (p<0.001). Angiogenesis grade was high in 64{\%} of active MM and 8{\%} of SMM/IMM, (p<0.001). The proportion of pts with a high(l) PCLI was 67{\%}, 9{\%}, 0{\%} for high, intermediate, and low grade angiogenesis respectively (p<0.001 ). No significant changes were observed in MVD following treatment; pre-treatment MVD and angiogenesis grade did not appear to be associated with response to therapy. Conclusions: Thal/Dex is strikingly effective as first line therapy (and an oral alternative to infusional VAD) for new, active MM. SMM/IMM pts also appear to achieve significant responses with Thai alone. However, these results are preliminary and responses/toxicities are still being evaluated and need further confirmation in the final analysis of this trial.",
author = "Rajkumar, {S Vincent} and S. Hayman and Rafael Fonseca and Angela Dispenzieri and Martha Lacy and S. Geyer and L. Wellik and Lust, {J. A.} and Kyle, {R. A.} and Greipp, {P. R.} and Witzig, {Thomas Elmer}",
year = "2000",
language = "English (US)",
volume = "96",
journal = "Blood",
issn = "0006-4971",
publisher = "American Society of Hematology",
number = "11 PART I",

}

TY - JOUR

T1 - Thalidomide plus dexamethasone (thal/dex) and thalidomide alone (thal) as first line therapy for newly diagnosed myeloma (mm)

AU - Rajkumar, S Vincent

AU - Hayman, S.

AU - Fonseca, Rafael

AU - Dispenzieri, Angela

AU - Lacy, Martha

AU - Geyer, S.

AU - Wellik, L.

AU - Lust, J. A.

AU - Kyle, R. A.

AU - Greipp, P. R.

AU - Witzig, Thomas Elmer

PY - 2000

Y1 - 2000

N2 - Background: A phase II trial of Thal/Dex combination and Thai as first line therapy in new untreated MM with laboratory correlative studies (interim analysis). Methods: Patients (pts) with active MM were treated with the Thal/Dex combination. Pts with smoldering or indolent MM (SMM/IMM) were treated with Thai alone. Thai was given orally at a dose of 200 mg/day for 2 weeks, and then increased as tolerated by 200 mg/day every 2 weeks to a maximum dose of 800 mg/day. Dex was given orally at a dose of 40 mg/day orally on days 1-4, 9-12, 17-20 (odd cycles) and 40 mg/day days 1-4 (even cycles) repeated monthly. Response was defined as a decrease in serum and urine monoclonal (M) protein by 50% or greater. Bone marrow (BM) microvessel density (MVD) using immunostaining for CD34 was estimated by determining the average number of vessels in 3 hot spots at 400x magnification. BM angiogenesis was also visually graded as low, intermediate and high. Results: 42 pts (26 with active MM and 16 with smoldering/indolent MM) were studied. In the Thal/Dex arm, 2 pts had grade 3-4 skin toxicity among the first 7 pts treated, at Thai dose of 400mg. The Thal/Dex arm was then amended to stop dose escalation, and keep Thai dose constant at 200mg. An objective response was seen in 20 pts (77%) with active MM treated with Thal/Dex. The response rate was 86% with Thai dose escalation (6 of 7 pts), and 74% with Thai dose constant at 200mg (14 of 19 pts). Major grade 3-4 toxicities were rash in 3 pts, and sedation, constipation and myalgias in 1 pt each. In the SMM/IMM arm, 6 pts (38%) achieved a response with Thai alone. Median pre-treatment MVD was 27 in the active MM arm, and 7 in the SMM/IMM arm (p<0.001). Angiogenesis grade was high in 64% of active MM and 8% of SMM/IMM, (p<0.001). The proportion of pts with a high(l) PCLI was 67%, 9%, 0% for high, intermediate, and low grade angiogenesis respectively (p<0.001 ). No significant changes were observed in MVD following treatment; pre-treatment MVD and angiogenesis grade did not appear to be associated with response to therapy. Conclusions: Thal/Dex is strikingly effective as first line therapy (and an oral alternative to infusional VAD) for new, active MM. SMM/IMM pts also appear to achieve significant responses with Thai alone. However, these results are preliminary and responses/toxicities are still being evaluated and need further confirmation in the final analysis of this trial.

AB - Background: A phase II trial of Thal/Dex combination and Thai as first line therapy in new untreated MM with laboratory correlative studies (interim analysis). Methods: Patients (pts) with active MM were treated with the Thal/Dex combination. Pts with smoldering or indolent MM (SMM/IMM) were treated with Thai alone. Thai was given orally at a dose of 200 mg/day for 2 weeks, and then increased as tolerated by 200 mg/day every 2 weeks to a maximum dose of 800 mg/day. Dex was given orally at a dose of 40 mg/day orally on days 1-4, 9-12, 17-20 (odd cycles) and 40 mg/day days 1-4 (even cycles) repeated monthly. Response was defined as a decrease in serum and urine monoclonal (M) protein by 50% or greater. Bone marrow (BM) microvessel density (MVD) using immunostaining for CD34 was estimated by determining the average number of vessels in 3 hot spots at 400x magnification. BM angiogenesis was also visually graded as low, intermediate and high. Results: 42 pts (26 with active MM and 16 with smoldering/indolent MM) were studied. In the Thal/Dex arm, 2 pts had grade 3-4 skin toxicity among the first 7 pts treated, at Thai dose of 400mg. The Thal/Dex arm was then amended to stop dose escalation, and keep Thai dose constant at 200mg. An objective response was seen in 20 pts (77%) with active MM treated with Thal/Dex. The response rate was 86% with Thai dose escalation (6 of 7 pts), and 74% with Thai dose constant at 200mg (14 of 19 pts). Major grade 3-4 toxicities were rash in 3 pts, and sedation, constipation and myalgias in 1 pt each. In the SMM/IMM arm, 6 pts (38%) achieved a response with Thai alone. Median pre-treatment MVD was 27 in the active MM arm, and 7 in the SMM/IMM arm (p<0.001). Angiogenesis grade was high in 64% of active MM and 8% of SMM/IMM, (p<0.001). The proportion of pts with a high(l) PCLI was 67%, 9%, 0% for high, intermediate, and low grade angiogenesis respectively (p<0.001 ). No significant changes were observed in MVD following treatment; pre-treatment MVD and angiogenesis grade did not appear to be associated with response to therapy. Conclusions: Thal/Dex is strikingly effective as first line therapy (and an oral alternative to infusional VAD) for new, active MM. SMM/IMM pts also appear to achieve significant responses with Thai alone. However, these results are preliminary and responses/toxicities are still being evaluated and need further confirmation in the final analysis of this trial.

UR - http://www.scopus.com/inward/record.url?scp=33748674849&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33748674849&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:33748674849

VL - 96

JO - Blood

JF - Blood

SN - 0006-4971

IS - 11 PART I

ER -