自家末梢血幹細胞移植後にタンデム移植がいいのか, VRD療法がいいのか,それともレナリドミド維持療法がいいのかの比較試験


J Clin Oncol. 2019 Jan 17


Autologous Transplantation, Consolidation, and Maintenance Therapy in Multiple Myeloma.

第3相臨床試験


AHCT+Len維持 vs AHCT + VRD4サイクル+ Len維持 vs AHCT + AHCT+Len維持


を比較した臨床試験

論文読む上での基礎情報

初発の多発性骨髄腫において自家末梢血幹細胞移植(AHCT)は従来の化学療法と比べて無増悪生存期間(PFS)および全生存期間(OS)を延長する.


(Blood 94:1248-1253, 1999)


(N Engl J Med 348:1875-1883, 2003)


(N Engl J Med 335:91-97, 1996)


自家末梢血幹細胞移植(AHCT)後のレナリドマイド(Len)の維持療法の追加はPFSとOSをさらに改善した.


(N Engl J Med 366:1770-1781, 2012)


(N Engl J Med 366:1782-1791, 2012)


(J Clin Oncol 35:3279-3289, 2017)




しかし,2回目のAHCT(いわゆるタンデム)をするべきか,するべきでないかはいまだに意見が分かれるところであり,よくわかっていない.

Clinical question

Key point

初回治療とそれに続く大量メルファランとAHCT,その後の2回目のAHCT+Len維持(タンデム後Len維持) or AHCT後4サイクルのVRD療法とそれに続くレナリドミド維持療法 or AHCT後レナリドミドの維持療法を比較した.


AHCT後レナリドミド維持療法群と比較して,タンデム群とVRD+Len維持療法群では38ヶ月でのPFSとOSを改善しなかった.


AHCT後のレナリドミド維持療法が依然としてスタンダードである.


AHCT後も38ヶ月の時点で80%以上生存しているのは,すばらしい結果である(★の進歩)

Abstract

目的

メルファラン200 mg / m 2と自家末梢血幹細胞移植(AHCT)、その後のレナリドマイド(len)維持療法は、移植適応多発性骨髄腫患者(MM)の無増悪生存期間(PFS)と全生存期間(OS)を改善した.


AHCT、タンデムAHCT(AHCT / AHCT)、およびAHCTとそれに続くlen維持療法、ボルテゾミブ、およびデキサメタゾンの4サイクル(RVD; AHCT + RVD)を比較することで、PFSを改善するための追加介入を試験する前向き無作為化第III相試験を計画した.


Single-cycle melphalan 200 mg/m2 and autologous hematopoietic cell transplantation (AHCT) followed by lenalidomide (len) maintenance have improved progression-free survival (PFS) and overall survival (OS) for transplantation-eligible patients with multiple myeloma (MM). We designed a prospective, randomized, phase III study to test additional interventions to improve PFS by comparing AHCT, tandem AHCT (AHCT/AHCT), and AHCT and four subsequent cycles of len, bortezomib, and dexamethasone (RVD; AHCT + RVD), all followed by len until disease progression.

方法

70歳以下の治療開始から12ヶ月以内に増悪のない症候性多発性骨髄腫患者が対象.


ランダムにAHCT / AHCT(タンデム) + len維持療法(n = 247)、AHCT + RVD + len維持療法(n = 254)、またはAHCT + len維持療法が割り当てられた(n = 257).


主要評価項目は38か月のPFSとした.


Patients with symptomatic MM within 12 months from starting therapy and without progression who were age 70 years or younger were randomly assigned to AHCT/AHCT + len (n = 247), AHCT + RVD + len (n = 254), or AHCT + len (n = 257). The primary end point was 38-month PFS.

結果

研究集団の年齢の中央値は56歳(20〜70歳)


患者の24%が高リスクMM、73%が初期治療として3剤併用療法、そして18%が登録時に完全奏効していた.

38ヶ月のPFS率は、


AHCT / AHCT + lenで 58.5% (95% CI,51.7% to 64.6%)


AHCT + RVD + lenで 57.8% (95% CI, 51.4% to 63.7%)


53.9%AHCT+Len維持療法 53.9% (95% CI, 47.4% to 60%) .

OSに関しては


AHCT / AHCT + len 81.8% (95% CI, 76.2% to 86.2%)、


AHCT + RVD + len 85.4% (95% CI, 80.4% to 89.3%)、


AHCT + len 83.7% (95% CI, 78.4% to 87.8%)


であった.

1年後のCR(complete response rates)は


AHCT / AHCT + len 50.5%(n = 192)


AHCT + RVD + len 58.4%(n = 209)


AHCT + len 83.7%4 7.1%(n = 208)

二次性悪性腫瘍の毒性プロファイルおよび発生は治療群間で同様であった.


The study population had a median age of 56 years (range, 20 to 70 years); 24% of patients had high-risk MM, 73% had a triple-drug regimen as initial therapy, and 18% were in complete response at enrollment. The 38-month PFS rate was 58.5% (95% CI, 51.7% to 64.6%) for AHCT/AHCT + len, 57.8% (95% CI, 51.4% to 63.7%) for AHCT + RVD + len, and 53.9% (95% CI, 47.4% to 60%) for AHCT + len. For AHCT/AHCT + len, AHCT + RVD + len, and AHCT + len, the OS rates were 81.8% (95% CI, 76.2% to 86.2%), 85.4% (95% CI, 80.4% to 89.3%), and 83.7% (95% CI, 78.4% to 87.8%), respectively, and the complete response rates at 1 year were 50.5% (n = 192), 58.4% (n = 209), and 47.1% (n = 208), respectively. Toxicity profiles and development of second primary malignancies were similar across treatment arms.

まとめ

Second AHCT or RVD consolidation as post-AHCT interventions for the up-front treatment of transplantation-eligible patients with MM did not improve PFS or OS. Single AHCT and len should remain as the standard approach for this population.

Table and Figure



原文

Abstract


PURPOSE:


Single-cycle melphalan 200 mg/m2 and autologous hematopoietic cell transplantation (AHCT) followed by lenalidomide (len) maintenance have improved progression-free survival (PFS) and overall survival (OS) for transplantation-eligible patients with multiple myeloma (MM). We designed a prospective, randomized, phase III study to test additional interventions to improve PFS by comparing AHCT, tandem AHCT (AHCT/AHCT), and AHCT and four subsequent cycles of len, bortezomib, and dexamethasone (RVD; AHCT + RVD), all followed by len until disease progression.


PATIENTS AND METHODS:


Patients with symptomatic MM within 12 months from starting therapy and without progression who were age 70 years or younger were randomly assigned to AHCT/AHCT + len (n = 247), AHCT + RVD + len (n = 254), or AHCT + len (n = 257). The primary end point was 38-month PFS.


RESULTS:


The study population had a median age of 56 years (range, 20 to 70 years); 24% of patients had high-risk MM, 73% had a triple-drug regimen as initial therapy, and 18% were in complete response at enrollment. The 38-month PFS rate was 58.5% (95% CI, 51.7% to 64.6%) for AHCT/AHCT + len, 57.8% (95% CI, 51.4% to 63.7%) for AHCT + RVD + len, and 53.9% (95% CI, 47.4% to 60%) for AHCT + len. For AHCT/AHCT + len, AHCT + RVD + len, and AHCT + len, the OS rates were 81.8% (95% CI, 76.2% to 86.2%), 85.4% (95% CI, 80.4% to 89.3%), and 83.7% (95% CI, 78.4% to 87.8%), respectively, and the complete response rates at 1 year were 50.5% (n = 192), 58.4% (n = 209), and 47.1% (n = 208), respectively. Toxicity profiles and development of second primary malignancies were similar across treatment arms.


CONCLUSION:


Second AHCT or RVD consolidation as post-AHCT interventions for the up-front treatment of transplantation-eligible patients with MM did not improve PFS or OS. Single AHCT and len should remain as the standard approach for this population.

コメントを残す

メールアドレスが公開されることはありません。

このサイトはスパムを低減するために Akismet を使っています。コメントデータの処理方法の詳細はこちらをご覧ください